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![SENSATION.
HEDIO.
alone is the source of salvation, and he is so every where,—these
were the two truths which he learned at Einsidlen, and they became
fundamental articles in his creed. The serious impression produced
on his soul soon manifested itself externally. Struck with the many
prevailing evils, he resolved to oppose them boldly. Not hesitating
between his conscience and his interest, he stood up openly, and, in
plain and energetic terms, attacked the superstition of the
surrounding crowds: Think not, said he from the pulpit, that God
is in this temple more than in any other part of his creation.
Whatever be the country in which you dwell, God encompasses you,
and hears you as well as in our Lady of Einsidlen. Can useless works,
long pilgrimages, offerings, images, the invocation of the Virgin, or
the saints, obtain the grace of God?... What avails the multitude of
words in which we embody our prayers? What avails a glossy hood—
a head well shaven—a long robe with its neat folds, and mules
caparisoned with gold? God looks to the heart, but our heart is
alienated from God.[670]
But Zuinglius wished to do more than lift his voice against
superstition. He wished to satisfy that eager longing for
reconciliation with God, felt by many of the pilgrims who had flocked
to the chapel of our Lady of Einsidlen. Christ, cried he, like a John
Baptist in this new wilderness of Judea, Christ, who was once
offered on the cross, is the expiatory victim, who, even through
eternity, makes satisfaction for the sins of all believers.[671] Thus
Zuinglius advanced. The day when this bold sermon was heard in
the most venerated sanctuary of Switzerland, the standard prepared
against Rome began to be more distinctly displayed on its mountain
heights, and there was, so to speak, a heaving of reform reaching
even to their deepest foundations.
In fact, universal astonishment seized the
multitude on hearing the discourse of the eloquent
priest. Some walked off in horror; others hesitated
between the faith of their fathers and the doctrine fitted to secure
their peace, while several came to Jesus Christ who was thus](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-31-320.jpg)
![ZUINGLIUS AND
THE LEGATES.
preached to them, and finding rest to their souls, took back the
tapers which they had intended to present to the Virgin. A crowd of
pilgrims returned to their homes, announcing every where what they
had heard at Einsidlen. Christ ALONE saves, and saves EVERYWHERE.
Bands, astonished at what they heard, stopped short without
finishing their pilgrimage. The worshippers of Mary diminished from
day to day. Their offerings formed almost the whole income of
Zuinglius and Geroldsek; but the intrepid witness of the truth felt
happy to be impoverished in order that souls might be spiritually
enriched.
During the feast of Pentecost, in the year 1518, among the
numerous hearers of Zuinglius, was a learned man of meek temper
and active charity, named Gaspard Hedio, doctor of theology at Bâle.
Zuinglius preached on the cure of the paralytic, (Luke, v,) where our
Saviour declares, The Son of Man hath power upon earth to forgive
sins, words well fitted to strike the crowd assembled in the Church
of the Virgin. The preacher roused, enraptured, and inflamed his
audience, especially the doctor from Bâle.[672] A long time after,
Hedio expressed his high admiration; How beautiful, said he, this
discourse, how profound, weighty, complete, penetrating, and
evangelical; how much it reminds one of the ενεργεια (energy) of
the ancient doctors.[673] From that moment Hedio admired and
loved Zuinglius.[674] He would fain have gone to him, and opened
his heart; he wandered around the abbey but durst not approach,
kept back, as he expresses it, by a superstitious timidity. He again
mounted his horse and slowly retired from our Lady, ever and again
turning his head to the spot which contained so great a treasure,
and feeling in his heart the keenest regret.[675]
Thus Zuinglius preached; less forcibly, no doubt,
than Luther, but with more moderation, and not
less success. He did nothing precipitately, and did
not come so violently into collision with men's minds as the Saxon
Reformer; he expected every thing from the power of truth. He](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-32-320.jpg)
![displayed the same wisdom in his relations with the heads of the
Church. Far from immediately declaring himself their enemy, he long
remained their friend. They were exceedingly indulgent to him, not
only because of his learning and talents, (Luther had the same
claims to the regard of the bishops of Mentz and Brandenburg,) but
especially because of his attachment to the pope's political party,
and the influence possessed by such a man as Zuinglius in a
republican state.
In fact, several cantons, disgusted with the service of the pope,
were disposed to break with him. But the legates flattered
themselves they might retain several of them by gaining Zuinglius,
as they gained Erasmus, with pensions and honours. At this time the
legates, Ennius and Pucci, went frequently to Einsidlen, where from
its proximity to the democratic cantons, it was more easy to carry on
negotiations with them. But Zuinglius, far from sacrificing the truth
to the demands and offers of Rome, omitted no opportunity of
defending the gospel. The famous Schinner, who had then some
disturbance in his diocese, passed some time at Einsidlen. The
whole papacy, said Zuinglius one day, rests on a bad foundation.
[676] Put your hand to the work, remove errors and abuses, or you
will see the whole edifice crumble to pieces with fearful uproar.[677]
He spoke with the same frankness to legate Pucci. Four times did he
return to the charge. With the help of God, said he to him, I will
continue to preach the gospel, and this preaching will shake Rome.
Then he pointed out to him what was necessary to save the Church.
Pucci promised every thing, but did nothing. Zuinglius declared that
he renounced the pension from the pope. The legate entreated him
to retain it; and Zuinglius, who at that time had no thought of
placing himself in open hostility to the head of the Church,
consented for three years to receive it. But think not, added he,
that for the love of money I retrench a single syllable of the truth.
[678] Pucci, alarmed, made the Reformer be appointed chaplain
acolyte to the pope. It was an avenue to new honours. Rome
thought to frighten Luther by sentences of condemnation, and to](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-33-320.jpg)
![STAPFER AND
ZUINGLIUS.
and ice coeval with the world. This avaricious band, in appearance
miserable enough, and not unlike a band of adventurers roaming for
plunder, walked in silence, amid the noise of the foaming torrents
which give rise to the Rhine, the Reuss, the Aar, the Rhone, the
Tessino, and other rivers, meditating how they were to plunder the
simple population of Helvetia. Samson (this was the Franciscan's
name) and his company first arrived in Uri, and there commenced
their traffic. They had soon done with these poor peasants, and
passed into the canton of Schwitz. Here Zuinglius was, and here the
combat between these two servants of two very different masters
was to take place. I can pardon all sins, said the Italian monk, the
Tezel of Switzerland. Heaven and hell are subject to my power, and
I sell the merits of Jesus Christ to whoever will purchase them, by
paying in cash for an indulgence.
Zuinglius heard of these discourses, and his zeal was inflamed.
He preached powerfully against them. Jesus
Christ, the Son of God, said he, thus speaks,
'Come unto ME, all ye that labour and are heavy
laden, and I will give you rest.' Is it not then audacious folly and
insensate temerity to say on the contrary, Purchase letters of
indulgence! run to Rome! give to the monks! sacrifice to the priests!
If you do these things I will absolve you from your sins![679] Jesus
Christ is the only offering; Jesus Christ is the only sacrifice; Jesus
Christ is the only way.[680]
Every body at Schwitz began to call Samson rogue and cheat. He
took the road to Zug, and for this time the two champions failed to
meet.
Scarcely had Samson left Schwitz when a citizen of this canton,
named Stapfer, a man of distinguished talent, and afterward
secretary of state, was with his family reduced to great distress.
Alas, said he, when applying in agony to Zuinglius, I know not
how to satisfy my own hunger and the hunger of my poor children.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-35-320.jpg)
![[681] Zuinglius knew to give where Rome knew to take; he was as
ready to practise good works, as to combat those who taught that
they were the means of obtaining salvation. He daily gave liberally to
Stapfer.[682] It is God, said he, anxious not to take any glory to
himself, It is God who begets charity in the believer, and gives him
at once the thought, the resolution, and the work itself. Whatever
good a righteous man does it is God who does it by his own power.
[683] Stapfer remained attached to him through life; and, four years
after, when he had become secretary of state, and felt wants of a
higher kind, he turned towards Zuinglius, and said to him with noble
candour, Since you provided for my temporal wants, how much
more may I now expect from you wherewith to appease the hunger
of my soul!
The friends of Zuinglius increased. Not only at Glaris, Bâle, and
Schwitz, did he find men of like spirit with himself; in Uri there was
the secretary of state, Schmidt; at Zug, Colin Müller and Werner
Steiner, his old companions in arms at Marignan: at Lucerne,
Xylotect and Kilchmeyer; Wittembach at Berne, and many others in
many other places. But the curate of Einsidlen had no more devoted
friend than Oswald Myconius. Oswald had quitted Bâle in 1516, to
take charge of the cathedral school at Zurich. In this town there
were no learned men, and no schools of learning. Oswald laboured
along with some well-disposed individuals, among others, Utinger,
notary to the pope, to raise the Zurich population out of ignorance
and initiate them in ancient literature. At the same time he defended
the immutable truth of the Holy Scriptures, and declared that if the
pope or emperor gave commands contrary to the gospel, obedience
was due to God alone, who is above both emperor and pope.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-36-320.jpg)
![CHAP. VI.
Zurich—The College of Canons—Election to the Cathedral—Fable
—Accusations—Confession of Zuinglius—The Designs of
God Unfolded—Farewell to Einsidlen—Arrival at Zurich—
Courageous Declaration of Zuinglius—First Sermons—
Effects—Opposition—Character of Zuinglius—Taste for
Music—Arrangement of the Day—Circulation by Hawkers.
Seven centuries had elapsed since Charlemagne had attached a
college of canons to this cathedral, over whose school Oswald
Myconius then presided. These canons having degenerated from
their first institution, and desiring in their benefices to enjoy the
sweets of indolence, elected a priest to preach and take the cure of
souls. This situation having become vacant some time after Oswald's
arrival, he immediately thought of his friend. What a prize it would
be for Zurich! Zuinglius' appearance was prepossessing. He was a
handsome man,[684] of graceful address, and pleasing manners. His
eloquence had already given him celebrity, while the lustre of his
genius made him conspicuous among all the confederates. Myconius
spoke of him to the provost of the chapter, Felix Frey, (who from the
appearance and talents of Zuinglius was already prepossessed in his
favour,)[685] to Utinger, an old man who was held in high respect,
and to canon Hoffman, a man of an upright open disposition, who,
having long preached against foreign service, was favourably
inclined to Ulric. Other Zurichers had, on different occasions, heard
Zuinglius at Einsidlen, and had returned full of admiration. The
election of preacher to the cathedral soon set all the inhabitants of
Zurich in motion. Different parties were formed. Several laboured
night and day for the election of the eloquent preacher of Our Lady
of the Eremites.[686] Myconius having informed his friend
—Wednesday next, replied Zuinglius, I will come and dine at](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-38-320.jpg)
![CHARGES
AGAINST
ZUINGLIUS.
Zurich, and talk over matters. He accordingly arrived. A canon to
whom he was paying a visit said to him, Could you come among us
to preach the word of God? I could, replied he; but will not come
unless I am called. He then returned to his abbey.
This visit spread alarm in the camp of his enemies.
Several priests were urged to apply for the
vacancy. A Suabian, named Laurent Fable, even
preached as a candidate, and the rumour went that
he was elected. It is then quite true, said Zuinglius, on learning it,
that a prophet has no honour in his own country, since a Suabian is
preferred to a Swiss. I know what value to set on popular applause.
[687] Zuinglius immediately after received a letter from the secretary
of Cardinal Schinner, informing him, that the election had not taken
place. But the false news which he had at first received nettled the
curate of Einsidlen. Knowing that a person so unworthy as this Fable
aspired to the place, he was more desirous to obtain it for himself,
and wrote about it to Myconius, who next day replied, Fable will
always continue fable: my masters have learned that he is already
the father of six boys, and possesses I know not how many
benefices.[688]
The enemies of Zuinglius did not abandon their opposition. All, it is
true, agreed in extolling his learning to the skies;[689] but said some,
He is too fond of music; others, He loves the world and pleasure;
others again, In early life he was too closely connected with giddy
companions. There was even one individual who charged him with
an instance of seduction. Zuinglius was not without blemish. Though
superior to the ecclesiastics of his time he more than once, in the
first years of his ministry, gave way to youthful propensities. It is
difficult to estimate the influence of an impure atmosphere on those
who live in it. There were in the papacy certain established
irregularities, allowed and sanctioned as conformable to the laws of
nature. A saying of Æneas Sylvius, afterwards pope under the name
of Pius II, gives an idea of the sad state of public morals at this](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-39-320.jpg)
![CONFESSION BY
ZUINGLIUS.
period. We give it in a note.[690] Disorder had become the rule,
order the exception.
Oswald displayed the greatest activity in favour of
his friend. He exerted all his powers in defending
him, and happily succeeded.[691] He went to
burgomaster Roust, to Hoffman, Frey, and Utinger. He praised
Zuinglius for his probity, honesty, and purity, and confirmed the
Zurichers in the favourable opinion which they had of the curate of
Einsidlen. Little credit was given to the speeches of his adversaries.
The most influential persons said, that Zuinglius should be preacher
at Zurich. The canons said so also, but in a whisper. Hope, wrote
Oswald to him with a full heart, for I hope. At the same time he
told him of the accusations of his enemies. Although Zuinglius was
not yet become altogether a new man, he belonged to the class of
those whose conscience is awakened, and who may fall into sin, but
never without a struggle, or without remorse. It had often been his
resolution to stand alone in the midst of the world, and maintain a
life of holiness. But when he saw himself accused, he did not
pretend to boast that he was without sin. Writing to canon Utinger,
he said, Having nobody to go along with me in the resolutions
which I had formed, several even of those about me, being offended
at them, alas! I fell, and like the dog of whom St. Peter speaks, (2
Ep. ii, 22,) returned to my vomit.[692] Ah! God knows with what
shame and anguish I have torn up these faults from the depths of
my heart, and laid them before Almighty God, to whom, however, I
would be less afraid to confess my misery than to mortal man.[693]
But while Zuinglius confessed himself to be a sinner, he, at the same
time vindicated himself from the most offensive charges which were
brought against him. He declared that he had ever abhorred the idea
of invading the sanctity of married life, or seducing innocence,[694]—
vices at that time but too common, or the truth of this, says he, I
appeal to all with whom I have lived.[695]](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-40-320.jpg)
![ARRIVAL AT
ZURICH.
The election took place on the 11th December, and out of the
twenty-four votes which were given, Zuinglius had seventeen. It was
time that the Reformation should begin in Switzerland. The chosen
instrument which Divine Providence had been preparing during three
years in the retreat of Einsidlen, was ready and must now be
translated elsewhere. God, who had chosen the new university of
Wittemberg, situated in the heart of Germany, and under the
protection of the wisest of princes, to call Luther thither, made
choice in Switzerland of the city of Zurich, regarded as the head of
the confederation, there to station Zuinglius, and to bring him into
contact not only with one of the most intelligent, simple, resolute,
and intrepid communities of Switzerland, but also with all the
cantons which are grouped around this ancient and powerful state.
The hand which had taken hold of a young shepherd of Sentis, and
led him to the school of Wesen, now brought him forward, powerful
in word and in deed, in the face of all, to regenerate his countrymen.
Zurich was about to become a focus of light to Switzerland.
The day which announced the election of Zuinglius
was to Einsidlen a day at once of joy and grief. The
circle which had been formed there was about to
be broken up by the withdrawal of its most valuable member, and
who could say whether superstition was not going again to take
possession of this ancient place of pilgrimage?... The council of state
in Schwitz conveyed the expression of its sentiments to Ulric by
designating him as reverend, learned, most gracious master, and
good friend.[696] At least do you yourself give us a successor
worthy of you, said Geroldsek in despair to Zuinglius. I have got
for you, replied he, a little lion, simple and wise; a man initiated in
the mysteries of sacred science. Let me have him, immediately
rejoined the administrator. It was Leo Juda, at once the gentle and
intrepid friend with whom Zuinglius had been so intimate at Bâle.
Leo accepted the call which brought him near his dear Ulric. Ulric
took farewell of his friends, quitted the solitude of Einsidlen, and
arrived at that delightful spot where, smiling and instinct with life,
rises the town of Zurich, surrounded by its amphitheatre of vine-clad](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-41-320.jpg)
![INSTRUCTIONS
OF THE
CHAPTER.
ZUINGLIUS'
DECLARATION.
hills, enamelled with meadows and orchards, crowned with forests,
and overtopped by the lofty peaks of the Albis.
Zurich, the centre of the political interests of Switzerland, where the
most influential persons in the nation frequently assembled, was the
place best fitted to act upon the whole country, and shed the seeds
of truth over all its cantons. Accordingly, the friends of letters and
the Bible hailed the appointment of Zuinglius with acclamation. At
Paris, in particular, the Swiss students, who were there in great
numbers, were enraptured with the news.[697] But if Zuinglius had
the prospect of a great victory at Zurich, he had also the prospect of
a severe contest. Glarean wrote him from Paris, I foresee that your
learning will stir up great enmity;[698] but be of good courage, and
you will, like Hercules, subdue monsters.[699]
On the 27th December, 1518, Zuinglius arrived at
Zurich, and took up his quarters at the hotel of
Einsidlen. He received a cordial and honourable
welcome. The chapter immediately met to receive
him, and invited him to take his seat in the midst
of them. Felix Frey presided; the canons, friendly
or hostile to Zuinglius, sat indiscriminately around their provost.
There was considerable excitement in the meeting; every one felt,
perhaps without distinctly acknowledging it to himself, how serious
the commencement of this ministry was likely to prove. Some
apprehension being entertained of the innovating spirit of the young
priest, it was agreed to set before him the most important duties of
his office. You will use your utmost endeavour, he was gravely told,
to secure payment of the revenues of the chapter, without
neglecting the least of them. You will exhort the faithful both from
the pulpit and in the confessional, to pay the first fruits and tithes,
and to show by their offerings that they love the Church. You will
make it your business to increase the revenues which are derived
from the sick, from sacrifices, and generally from every ecclesiastical
act. The chapter added, As to the administration of the
sacraments, preaching, and personal presence, amid the flock, these](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-42-320.jpg)
![ZUINGLIUS'
FIRST SERMONS
AT ZURICH.
too are duties of the priest. However, in these different respects, and
particularly in regard to preaching, you may supply your place by a
vicar. You should administer the sacraments only to persons of
distinction, and after being requested. You are expressly forbidden
to do it to all persons indiscriminately.[700]
Strange rule to be given to Zuinglius! Money,
money, still money!... Was it then for this that
Christ established his ministry? Still prudence
tempers his zeal; he knows that we cannot all at
once deposit the seed in the ground, see the growth of the tree, and
gather its fruit. Zuinglius, therefore, without explaining his views on
what was enjoined him, humbly expressed his gratitude for the
honourable appointment which he had received, and stated what he
calculated on being able to do. The life of Jesus, said he, has
been too long hidden from the people. I will preach on the whole
gospel of St. Matthew, chapter by chapter, following the mind of the
Holy Spirit, drawing only at the well-springs of Scripture,[701] digging
deep into it, and seeking the understanding of it by persevering
fervent prayer.[702] I will consecrate my ministry to the glory of God;
the praise of His only Son; the real salvation of souls, and their
instruction in the true faith.[703] This new language made a deep
impression on the chapter. Some expressed joy, but the majority
openly disapproved.[704] This mode of preaching is an innovation,
exclaimed they, this innovation will soon lead to others, and where
is it to stop? Canon Hoffman in particular thought it his duty to
prevent the fatal effects of a choice which he had himself
patronised. This exposition of Scripture, said he, will be more
hurtful than useful to the people. It is not a new method, replied
Zuinglius, it is the ancient method. Recollect the homilies of St.
Chrysostom on St. Matthew, and of St. Augustine on St. John.
Besides, I will use moderation, and give none any reason to
complain.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-43-320.jpg)
![Thus Zuinglius abandoned the exclusive use of fragments of the
gospel as practised since the days of Charlemagne; re-establishing
the Scripture in its ancient rights, he, from the commencement of his
ministry, united the Reformation to the primitive ages of Christianity,
and prepared a more profound study of the Word of God for ages to
come. But he did more. The strong and independent position which
he took up in the face of the Church showed that the work in which
he had engaged was new. The figure of the Reformer stood out in
bold relief to the public eye, and the Reformation advanced.
Hoffman, having failed in the chapter, addressed a written request to
the provost to prohibit Zuinglius from shaking the popular belief. The
provost sent for the new preacher, and spoke to him with great
kindness. But no human power could close his lips. On the 31st
December, he wrote to the council of Glaris, that he entirely resigned
the cure of souls which had hitherto been reserved for him, and
gave himself wholly to Zurich, and to the work which God was
preparing for him in this town.
On Saturday, being new-year's-day, and also the birthday of
Zuinglius, who had completed his thirty-fifth year, he mounted the
pulpit of the cathedral. A great crowd, eager to see a man who had
already acquired so much celebrity, and to hear this new gospel, of
which every one began to speak, filled the church. It is to Christ,
said Zuinglius, that I wish to conduct you; to Christ, the true source
of salvation. His divine word is the only nourishment which I would
give to your heart and life. Then he announced that to-morrow, the
first Sunday of the year, he would begin to expound the gospel
according to St. Matthew. Accordingly, the preacher, and a still larger
audience than the day before, were at their posts. Zuinglius opened
the gospel—the gospel which had so long been a sealed book—and
read the first page, going over the history of the patriarchs and
prophets mentioned in the first chapter of St. Matthew, and
expounding it in such a way that all were astonished and delighted,
and exclaimed, We never heard anything like this.[705]](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-44-320.jpg)
![THEIR EFFECTS.
He continued thus to expound St. Matthew,
according to the original Greek. He showed how
the whole Bible found at once its exposition and its
application in the very nature of man. Delivering the loftiest truths of
the gospel in simple language, his preaching reached all classes, the
learned and the wise, as well as the ignorant and simple.[706] He
extolled the infinite mercies of God the Father, and implored all his
hearers to put their confidence in Jesus Christ alone as the only
Saviour.[707] At the same time, he earnestly called them to
repentance; forcibly attacked the errors which prevailed among the
people; fearlessly rebuked luxury, intemperance, extravagance in
dress, the oppression of the poor, idleness, foreign service, and
foreign pensions. In the pulpit, says one of his companions, he
spared no one, pope, emperor, kings, dukes, princes, lords, not even
the confederates. All his energy, and all the joy of his heart were in
God: accordingly he exhorted all the inhabitants of Zurich to put
their confidence in Him only.[708] Never was man heard to speak
with so much authority, says Oswald Myconius, who with joy and
high hopes watched the labours of his friend.
The gospel could not be preached in vain in Zurich. A continually
increasing multitude of men of all classes, and more especially of the
common people, flocked to hear him.[709] Several Zurichers had
ceased to attend on public worship. I derive no benefit from the
discourses of these priests, often exclaimed Füsslin, a poet,
historian, and counsellor of state; they do not preach the things of
salvation; for they do not comprehend them. I see nothing in them
but covetousness and voluptuousness. Henry Räuschlin, treasurer
of state, one who diligently read the Scriptures, was of the same
opinion: The priests, said he, met in thousands at the Council of
Constance ... to burn the best man among them. These
distinguished men, led by curiosity, went to hear Zuinglius' first
sermon. Their countenances bespoke the emotion with which they
followed the orator. Glory to God! said they, on coming out; this is
a preacher of the truth. He will be our Moses to deliver us from](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-45-320.jpg)
![OPPOSITION.
Egyptian darkness.[710] From this moment they became the
Reformer's intimate friends. Powers of the world, said Füsslin,
cease to proscribe the doctrine of Christ! After Christ the Son of
God was put to death, sinners were raised up. And now, should you
destroy the preachers of truth, you will see their places supplied by
glaziers, carpenters, potters, founders, shoemakers, and tailors, who
will teach with power.[711]
In Zurich, at the outset, there was only one shout
of admiration, but when the first moment of
enthusiasm was over, the adversary resumed
courage. Worthy persons alarmed at the idea of a Reformation,
gradually drew off from Zuinglius. The violence of the monks which
had been veiled for an instant, reappeared, and the college of
canons resounded with complaints. Zuinglius stood immovable. His
friends beholding his courage, felt in his presence as if a man of
apostolic times had reappeared.[712] Among his enemies, some
scoffed and jeered; others uttered insulting menaces, but he
endured all with Christian patience.[713] Whoso, he was wont to
say, would gain the wicked to Jesus Christ must wink at many
things,[714]—an admirable saying which ought not to be lost sight
of.
His character and general bearing towards all contributed as much
as his discourses to win their hearts. He was at once a true Christian
and a true republican. The equality of mankind was not with him a
mere watchword; it was written on his heart and manifested in his
life. He had neither that pharisaical pride, nor that monastic
gruffness, which are equally offensive to the simple and the wise of
the world. Men were drawn towards him, and felt at ease when
conversing with him. Strong and mighty in the pulpit, he was affable
to all whom he met in the streets, or in the public squares. At the
places where the merchants or incorporations met he was often
seen among the citizens expounding the leading points of Christian
doctrine, or conversing familiarly with them. He gave the same](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-46-320.jpg)
![TASTE FOR
MUSIC.
STUDIOUS
HABITS.
cordial reception to peasant and patrician. He invited country folks
to dine with him, says one of his bitterest enemies, walked with
them, spoke to them of God, made the devil enter into their hearts
and his writings into their pockets. He even went so far that the
leading persons in Zurich visited those peasants, entertained them,
and walked over the town with them, showing them all sorts of
attention.[715]
He continued to cultivate music with moderation,
says Bullinger: nevertheless the enemies of the
gospel took advantage of it, and called him The
evangelical flute and lute player.[716] Faber having
one day reproached him with his fondness for
music, Zuinglius, with noble candour, replied, My dear Faber, you
know not what music is. I have, it is true, learned to play on the
lute, the violin, and other instruments, and am able by these means
to pacify little children;[717] but you of course are too holy for music.
Do you not know that David was a skilful player on the harp, and in
this way drove the evil spirit out of Saul? ... Ah! if you knew the
sound of the heavenly lute, the evil spirit of ambition and avarice by
which you are possessed would come out of you also. Perhaps this
was Zuinglius' foible, though it was in a spirit of cheerfulness and
Christian liberty that he cultivated this art, which religion has always
associated with her sublimest flights. He set some of his Christian
poems to music, and did not scruple sometimes to amuse the
youngest of his flock with his lute. He showed the same good nature
to the poor. He ate and drank, says one of his contemporaries,
with all who invited him,—he despised no one; he was most
compassionate to the poor; always firm and always joyful in bad as
in good fortune. No evil made him afraid; his words were at all times
full of energy, and his heart full of consolation.[718] Thus Zuinglius
increased in popularity—after the example of his Master, seated
alternately at the table of the common people and the banquet of
the great, but still constantly intent on the work to which God had
called him.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-47-320.jpg)
![INDULGENCES.
At the same time he was an indefatigable student. In the morning,
till ten, he read, wrote, and translated: Hebrew in particular engaged
his attention. After dinner he attended to those who had any thing
to tell him, or any advice to ask of him: took a walk with his friends
and visited his hearers. At two he resumed his studies. He took a
short walk after supper, and afterwards wrote letters which often
occupied him till midnight. He always stood when he studied, and
did not allow himself to be interrupted unless on important business.
[719]
But the labours of a single individual were not
sufficient. A person, named Lucian, one day came
to him with the writings of the German Reformer.
He had been sent by Rhenan, a learned man, then resident at Bâle,
and indefatigable in circulating the Reformer's writings throughout
Switzerland. Rhenan had become aware that the hawking of books
was an important means of diffusing evangelical doctrine. Lucian
had travelled almost over the whole of Switzerland, and knew
everybody. See, said Rhenan to Zuinglius, whether this Lucian has
the necessary prudence and ability; if he has, let him go from town
to town, burgh to burgh, village to village, and even from house to
house, among the Swiss, with Luther's writings, especially his
exposition on the Lord's Prayer, written for the laity.[720] The more
he is known the more purchasers will he find. But care must be
taken not to let him hawk other books. If he has none but Luther's,
his sale of them will be the greater. Thus the humble roof of many a
Swiss family was penetrated with some rays of light. There was one
other book, however, which Zuinglius should have caused to be
hawked with those of Luther—the Gospel of Jesus Christ.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-48-320.jpg)
![you my dapple grey horse in exchange. It was a high price for the
horse, but the courser pleased the Franciscan, and the bargain was
struck. The horse went to the monk's stable, and all these souls
were declared for ever exempted from hell.[721] Another day, he give
a burgher, for thirteen florins, an indulgence, in virtue of which his
confessor was authorised to absolve him from any species of perjury.
[722] So much was Samson in repute, that Counsellor May, an
enlightened old man, having said something against him, was
obliged to go down on his knees, and ask pardon of the arrogant
monk.
This was the monk's last day, and a loud ringing of bells announced
his immediate departure from Berne. Samson was in the church
standing on the steps of the high altar. Canon Henry Lupulus,
formerly Zuinglius's master, was acting as his interpreter. When the
wolf and the fox rendezvous together in the field, said canon
Anselm, turning to the Schulthess of Walleville, the best thing for
you, worthy Sir, is to put your sheep and geese in safety. But the
monk cared little for these sarcasms, which, besides, did not reach
his ear. Kneel, said he to the superstitious crowd, repeat three
Paters, three Ave Marias, and your souls will forthwith be as pure as
at the moment of baptism. Then all the people fell upon their
knees. Samson wishing even to outdo himself, exclaimed, I deliver
from the torments of purgatory and hell all the spirits of the
departed Bernese, whatever may have been the manner and place
of their death. These jugglers, like those at fairs, kept their finest
feat for the last.
Samson set out with a heavy purse towards Zurich, crossing Argovia
and Baden. The farther on he got, the monk, whose appearance on
passing the Alps was so shabby, proceeded with more pride and
splendour. The Bishop of Constance, irritated that Samson had not
employed him to legalise his bulls, had forbidden all the curates of
his diocese to open their churches to him. At Baden, nevertheless,
the curate durst not long oppose his traffic. This redoubled the
monk's effrontery. Making the round of the burying ground at the](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-50-320.jpg)
![THE DEAN OF
BREMGARTEN.
HENRY
BULLINGER.
head of a procession, he seemed to fix his eyes on some object in
the air, while his acolytes sung the hymn for the dead, and
pretending to see souls flying from the burying ground to heaven, he
exclaimed—Ecce volant! See how they fly. One day, an inhabitant
of the place getting up into the church steeple, a great number of
feathers were soon seen in the air falling down on the astonished
procession; See how they fly, exclaimed the wag of Baden, shaking
a feather cushion from the steeple. Many began to laugh.[723]
Samson fell into a rage, and could not be appeased till he learned
that the individual was subject to fits of derangement: he left Baden
in a huff.
Continuing his journey, he arrived, towards the end
of February, 1519, at Bremgarten, at the
solicitation of the Schulthess and second curate,
who had seen him at Baden. No individual in that
district had a higher reputation than dean Bullinger
of Bremgarten. Though far from enlightened as to the errors of the
Church and the Word of God, being open, zealous, eloquent, kind to
the poor, and ready to do a service to the humblest, he was loved by
every body. He had in his youth formed a connection with the
daughter of a counsellor of the place. This was the usual expedient
of such of the priests as were unwilling to live in general
licentiousness. Anna had borne him five sons, but this had in no way
lessened the respect which the dean enjoyed. There was not in
Switzerland a more hospitable house than his. A great lover of the
chace, he was seen surrounded with ten or twelve dogs, and
accompanied by the barons of Hallwyll, the abbot Mury, and the
gentry of Zurich, scouring the fields and forests around. He kept
open table, and none of his guests was more jovial than himself.
When the deputies to the Diet were on their way to Baden, on
passing through Bremgarten they failed not to take their seats at the
dean's table. Bullinger, said they, keeps court like the most
powerful baron.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-51-320.jpg)
![SAMSON AND
THE DEAN.
In this house strangers remarked a child of an
intelligent countenance. Henry, one of the dean's
sons, from his earliest years, had many narrow
escapes. Having been seized with the plague, preparations were
making for his funeral when he showed some signs of life, and was
restored to his delighted parents. On another occasion, a wandering
beggar, having won him by caresses, was carrying him off from his
family, when some persons in passing recognised and rescued him.
At three years of age he could repeat the Lord's prayer and the
apostles' creed. One day having slipt into the church, he got into his
father's pulpit, stood up gravely, and at the full stretch of his voice,
cried out, I believe in God the Father, and so on. At twelve, he was
sent to the Latin school of Emmeric, his heart overwhelmed with
fear; for those times were dangerous for a young boy without
experience. When the students of an university thought its discipline
too severe, they not unfrequently left it in troops, carrying the
children with them, and encamped in the woods, from which they
sent the youngest of their number to beg, or sometimes with arms
in their hands they rushed forth on the passing traveller, robbed him,
and then consumed their booty in debauchery. Henry was happily
kept from evil in this distant abode. Like Luther, he gained his
livelihood by singing before the houses, for his father wished to
teach him to live by his own shifts. He was sixteen when he opened
a New Testament. I found in it, says he, every thing necessary for
man's salvation, and thenceforth I laid it down as a principle to
follow the Holy Scriptures alone, and reject all human additions. I
believe neither the fathers nor myself, but explain Scripture by
Scripture, without adding any thing or taking any thing away.[724]
God was thus preparing this young man who was one day to
succeed Zuinglius. He is the author of the manuscript journal which
we often quote.
About this time Samson arrived at Bremgarten with all his train. The
bold dean undismayed by this petty Italian army, prohibited the
monk from vending his wares in his neighbourhood. The Schulthess,
town clerk, and second pastor, Samson's friends, had met in a room](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-52-320.jpg)
![INTERNAL
WRESTLINGS OF
ZUINGLIUS.
of the inn at which he had alighted, and were standing quite
disconcerted around the impatient monk. The dean arrived—Here
are the papal bulls, said the monk to him, open your church.
The Dean.—I will not allow the purses of my parishioners to be
emptied by means of letters not authenticated, for the bishop
has not legalised them.
The Monk (in a solemn tone).—The pope is above the bishop. I
enjoin you not to deprive your flock of this distinguished grace.
The Dean.—Should it cost me my life, I won't open my
church.
The Monk (with indignation).—Rebellious priest! in the name of
our most holy lord the pope, I pronounce against you the
greater excommunication, and will not absolve you till you
ransom your unheard-of audacity at the price of three hundred
ducats....
The Dean (turning on his heel and retiring).—I will know how
to answer before my lawful judges: as for you and your
excommunication I have nothing to do with them.
The Monk (transported with rage).—Impudent brute! I am on
my way to Zurich, and will there lay my complaint before the
deputies of the Confederation.[725]
The Dean.—I can appear there as well as you, and this instant
I set out.
While these things were taking place at
Bremgarten, Zuinglius, who saw the enemy
gradually approaching, kept preaching vigorously
against indulgences.[726] Vicar Faber of Constance
encouraged him, promising him the bishop's support.[727] I know,
said Samson, while proceeding towards Zurich, that Zuinglius will
attack me, but I will stop his mouth. Zuinglius was in truth too](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-53-320.jpg)
![much alive to the value of pardon by Christ not to attack the paper
indulgences of these men. Often, like Luther, he trembled because of
sin; but in the Saviour found deliverance from his fears. This modest
but brave man was advancing in the knowledge of God. When
Satan frightens me, said he, by crying to me: You do not this, and
you do not that, and yet God commands them!—immediately the
soft voice of the gospel consoles me, saying: What thou canst not do
(and assuredly thou canst do nothing,) Christ does for thee. Yes,
continues the pious evangelist, when my heart is agonised because
of my powerlessness, and the feebleness of my flesh, my spirit
revives at the sound of this glad news: Christ is thy innocence! Christ
is thy righteousness! Christ is thy salvation! Thou art nothing, thou
canst do nothing! Christ is the Alpha and the Omega! Christ is all,
and can do all.[728] All created things will forsake and deceive thee,
but Christ, the Holy and Righteous One, will receive and justify
thee.... Yes, exclaims Zuinglius, He is our righteousness, and the
righteousness of all who shall ever appear as righteous before the
judgment seat of God!...
Indulgences could not stand a moment when confronted with such
truths; and hence Zuinglius never hesitated to attack them. No
man, said he, is able to forgive sins. Christ alone, very God and
very man, is able to do it.[729] Go, buy indulgences ... but rest
assured you are not at all forgiven. Those who vend forgiveness of
sins for money are the companions of Simon Magus, the friends of
Balaam and the ambassadors of Satan.
Dean Bullinger, still warm from his conference with the monk, arrived
at Zurich before him. He came to complain to the Diet against this
shameless dealer and his traffic. Envoys from the bishop had arrived
for the same purpose. They made common cause, and promised to
support each other. The spirit which animated Zuinglius breathed
upon this town, and the council of State resolved to oppose the
monk's entry into Zurich.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-54-320.jpg)
![SAMSON
DISMISSED.
Samson had arrived in the suburbs, and alighted at
an inn. One foot was already on the stirrup
preparatory to his entry, when deputies from the
council arrived, and while making the customary offer of wine to him
as a papal envoy, intimated to him that he might dispense with
appearing in Zurich. I have something to communicate to the Diet
in the name of his holiness, replied the monk. It was a trick.
However, it was resolved to admit him; but as he spoke only of his
bulls he was dismissed, after being compelled to retract the
excommunication which he had pronounced against the dean of
Bremgarton. He went off in a rage, and the pope shortly after
recalled him to Italy. A car drawn by three horses, and loaded with
the money of which his lies had robbed the poor, preceded him on
the steep tracts of St. Gothard, which eight months before he had
crossed in poverty, without style, merely the bearer of a few papers.
[730]
On this occasion the Helvetic showed more firmness than the
Germanic Diet. The reason was, because no cardinals and bishops
sat in it. Hence the pope deprived of these supports dealt more
gently with Switzerland than Germany. In other respects, the affair
of indulgences, which played so important a part in the Reformation
of Germany, is only an episode in that of Switzerland.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-55-320.jpg)
![GOD'S TIME
CHAP. VIII.
The Labours of Zuinglius—The Baths of Pfeffers—God's time—
The Great Death—Zuinglius seized with the Plague—His
Enemies—His Friends—Convalescence—General Joy—Effect
of the Plague—Myconius at Lucerne—Oswald encourages
Zuinglius—Zuinglius at Bâle—Capito called to Mentz—Hedio
at Bâle—An Unnatural Son—Preparation for Battle.
Zuinglius did not spare himself. His many labours called for some
relaxation, and he was ordered to the baths of Pfeffers. Ah! said
Herus, one of the pupils who lodged with him, and who thus
expressed the feeling of all who knew Zuinglius, had I a hundred
tongues, a hundred mouths, a brazen throat, as Virgil expresses it;
or rather had I the eloquence of Cicero, how could I express all I
owe you, and all that I feel at this separation.[731] Zuinglius,
however, set out and reached Pfeffers through the astonishing gorge
formed by the impetuous torrent of the Jamina. He descended into
that infernal abyss, as the hermit David called it, and arrived at the
baths, which are perpetually agitated by the dashing of the torrent,
and bedewed by the spray of its foaming water. Where Zuinglius
lodged it was so dark that candles were burnt at mid-day. He was
even assured by the inmates, that frightful phantoms sometimes
appeared in the darkness.
Even here Zuinglius found opportunity to serve his
Master. His affability won the heart of several of the
patients, among others a celebrated poet, Philip
Ingentinus, professor at Friburg, in Brigau,[732] who thenceforward
became a zealous supporter of the Reformation.
God watched over his own work, and was pleased to hasten it.
Zuinglius' defect lay in his strength. Strong in body, strong in](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-56-320.jpg)
![ZUINGLIUS
ATTACKED BY
THE PLAGUE.
character, strong in talents, he was to see all these varieties of
strength broken, that he might thereby become such an instrument
as God loves to employ. He stood in need of a baptism, that of
adversity, infirmity, feebleness, and pain. Such a baptism Luther had
received at that period of agony when the cell and long passages of
the convent of Erfurt resounded with his cries. Zuinglius was to
receive it by being brought into contact with sickness and death. The
heroes of this world—the Charles Twelfths and Napoleons—have a
moment which is decisive of their career and their glory, and it is
when they all at once become conscious of their strength. There is
an analogous moment in the life of God's heroes, but it is in a
contrary direction; it is when they recognise their impotence and
nothingness; thenceforth they receive strength from on high. Such a
work as that of which Zuinglius was to be the instrument is never
accomplished by man's natural strength; it would immediately wither
away like a tree transplanted after its full growth, and when in full
leaf. A plant must be feeble in order to take root, and a grain of corn
must die in the ground before it can yield a full return. God led
Zuinglius, and with him the work of which he was the stay, to the
gates of the grave. It is from among bones and darkness, and the
dust of the dead, that God is pleased to take the instruments, by
means of which he illumines, regenerates, and revives the earth.
Zuinglius was hidden among the immense rocks
which hem in the furious torrent of the Jamina,
when he unexpectedly learned that the plague, or
as it was termed the great death,[733] was at
Zurich. This dreadful scourge broke out in August, on St. Lawrence
day, lasted till Candlemas, and carried off two thousand five hundred
persons. The young people who lodged with Zuinglius had
immediately left, conformably to directions which he had given. His
house was empty, but it was to him the very moment to return. He
hurriedly quitted Pfeffers, and reappearing in the bosom of his flock,
now decimated by the plague, he immediately sent to Wildhaus for
his young brother Andrew, who wished to attend him. From that
moment he devoted himself entirely to the victims of this dreadful](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-57-320.jpg)
![scourge. Every day he preached Christ and his consolations to the
sick.[734] His friends delighted to see him safe and sound in the
midst of so many fatal darts,[735] still felt a secret alarm. Conrad
Brunner, who himself died of the plague a few months after, writing
him from Bâle said; Do good, but at the same time remember to
take care of your life. It was too late: Zuinglius was seized with the
plague. The great preacher of Switzerland was stretched on a bed
from which, perhaps, he was never again to rise. He communed with
himself, and turned his eye heavenward. He knew that Christ had
given him a sure inheritance, and disclosing the feelings of his heart
in a hymn remarkable for unction and simplicity, of which, not being
able to give the antique and expressive phraseology, we have
endeavoured to preserve the rhythm and literal meaning, he
exclaimed:—
My door has opened ...
Death appears.[736]
My God! my strength!
Dispel all fears!
Oh, Jesus! raise
Thy pierced arm,
And break the sword
That caused alarm.
But if my soul
In life's mid-day
Thy voice recalls,[737]
Then I obey.
Ah! let me die,
For I am thine;
Thy mansions wait
Such faith as mine.](https://image.slidesharecdn.com/61609-250628092129-9c2261d2/85/Integrin-and-Cell-Adhesion-Molecules-Methods-and-Protocols-1st-Edition-Alexandre-Chigaev-58-320.jpg)
Integrin and Cell Adhesion Molecules Methods and Protocols 1st Edition Alexandre Chigaev
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- 6. Me t h o d s i n Mo l e c u l a r Bi o l o g y ™ Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651
- 8. Integrin and Cell Adhesion Molecules Methods and Protocols Edited by Motomu Shimaoka ImmuneDiseaseInstitute,PrograminCellularandMolecularMedicineatChildren’sHospitalBoston, DepartmentofAnesthesia,HarvardMedicalSchool,Boston,MA,USA; DepartmentofMolecularPathobiologyandCellAdhesionBiology,MieUniversityGraduateSchool ofMedicine,Tsu-City,Mie,JAPAN
- 9. Editor Motomu Shimaoka Immune Disease Institute Program in Cellular and Molecular Medicine at Children’s Hospital Boston Department of Anesthesia Harvard Medical School Boston, MA, USA and Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu-City, Mie, JAPAN shimaoka@idi.harvard.edu shimaoka@doc.medic.mie-u.ac.jp ISSN 1064-3745 e-ISSN 1940-6029 ISBN 978-1-61779-165-9 e-ISBN 978-1-61779-166-6 DOI 10.1007/978-1-61779-166-6 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011930756 © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com)
- 10. v Preface Integrins are the foremost and largest family of cell adhesion molecules with noncova- lently associated a and b subunits that mediate cell–cell and cell–extracellular matrix inter- actions. To date, 19 different integrin a subunits and 8 different integrin b subunits have been reported in vertebrates, forming at least 24 a/b heterodimers and representing the most structurally and functionally diverse cell adhesion molecules. As their name implies, integrins create an integrated connection between the cytoskeleton and attachment points in the extracellular microenvironment, where they mediate force-resistant adhesion, polar- ization, and cell migration. Integrins play pivotal roles across not only a wide range of physiological processes including tissue morphogenesis, immune responses, wound heal- ing, and regulation of cell growth and differentiation, but also in numerous pathological phenomena such as autoimmunity, thrombosis, and cancer metastasis/progression. Therefore, investigations on integrins often demand multidisciplinary approaches, making researchers long for a handy collection of comprehensive and practical protocols that detail experimental methods for studying integrin and related cell-adhesion molecule functionality. Integrins and Cell Adhesion Molecules: Methods and Protocols is, hence, of great interest to a broad readership, from cell biologists and immunologists to cancer researchers, as well as from molecular and structural biologists to biochemists. The aim of the second edition of Integrins and Cell Adhesion Molecules: Methods and Protocols (f/k/a Integrin Protocols) is to provide readers not only with basic protocols in studying integrin functions, but also with summaries on those state-of-the-art technologies that have been utilized for understanding integrin functionality at the cellular, molecular, structural, and organismal levels. Part I of this book (Chapters 1–6) contains basic protocols for the study of integrin and related cell-adhesion molecule functionality in vitro. To open Part I, Chigaev and Sklar provide an overview of several experimental procedures used for investigating integrin-dependent cell adhesion (Chapter 1). The cell-adhesion assay is a standard and important experimental procedure to examine the adhesiveness of cells to substrates. Weitz-Schmidt and Chreng detail a protocol of a convenient and highly reproducible cell-adhesion assay using a V-bottom-shaped plate (Chapter 2). Although integrins are the major receptors that, in many aspects, regulate cell migration, the migration of certain cell types in the interstitial space requires either a lesser degree of integrin involvement or none at all. Shulman and Alon describe real-time assays for the study of integrin- dependent and independent cell migration (Chapter 3). Efficient transduction methods are required for facilitating the close examination of integrin functionality in primary lym- phocytes. Banerjee and Shimaoka introduce a simple protocol for lentivirus-mediated gene transduction in primary T cells (Chapter 4). To better understand integrin-ligand interactions, biochemical assays using purified integrin proteins or integrin domains are essential. Vorup-Jensen discusses an application of surface plasmon resonance biosensing to study the complex ligand-binding kinetics of the integrin aX I domain (Chapter 5). In addition, Yuki presents plate- and bead-based assays to investigate the ligand-binding abilities of purified integrin LFA-1 protein (Chapter 6).
- 11. vi Preface Part II (Chapters 7–11) illustrates structural biology approaches for studying integ- rins and related cell-adhesion molecules. At the beginning of Part II, Fu, Wang, and Luo provide a comprehensive review of integrin domains and conformational regulation (Chapter 7). Protein expression remains a formidably difficult obstacle in determining the crystal structures of many integrin–ligand complexes. Zhang and Wang describe a proto- col to express and purify integrin I domains and IgSF ligands for crystallography (Chapter 8). Electron microscopy has been successfully used to understand how integrin conforma- tions are globally changed. Iwasaki discusses an application of electron microscopic imag- ing that tackles the conformational flexibility of integrins (Chapter 9). NMR is a powerful technique to study protein–protein interactions. Nishida and Shimada describe a novel NMR method, termed the cross-saturation (CS) method, and its application in studying the ligand-binding activities of cell-adhesion molecules (Chapter 10). Elucidating the bio- physical properties of individual adhesion molecules demands the use of single-molecule techniques. Seog utilizes two important single-molecule techniques, atomic force micros- copy and optical tweezing, to examine cell-adhesion molecules (Chapter 11). Part III (Chapters 12–16) focuses on emerging imaging technologies for investigat- ing cell migration. Part III begins with Carman’s comprehensive overview of imaging in the study of integrins (Chapter 12). Analysis of cell motility and migration is one of the most important fields to which imaging technologies have greatly contributed. Wiemer, Wernimont, and Huttenlocher describe methods for live time-lapse imaging of T-cell migration on ICAM-1 substrates (Chapter 13). Fluorescence resonance energy transfer (FRET) has emerged as a powerful research tool for investigating integrin conformational changes in living cells. Lefort, Hyun, and Kim utilize FRET to monitor structural altera- tions during integrin activation in leukocytes (Chapter 14). Recent technological advance- ments in optics and fluorescent dyes have enabled high-resolution imaging of the contact interface between adherent leukocytes and endothelial cells. Carman details a protocol for high-resolution fluorescence microscopy in the study of transendothelial migration (Chapter 15). Two-photon intravital imaging has revolutionized our understanding of how immune cells behave and move in living animals. Murooka and Mempel discuss an application of multiphoton intravital microscopy to study lymphocyte motility in the lymph nodes of living mice (Chapter 16). Part IV (Chapters 17–21) presents strategies to elucidate signaling through cell- adhesion molecules. To open Part IV, Kinashi comprehensively reviews integrin signal- ing (Chapter 17). Rap1 GTPase is a key signaling molecule in integrin activation. Katagiri and Kinashi discuss the roles of Rap1 in integrin inside-out signaling and cell polarity, as well as experimental procedures to study Rap1 functionality (Chapter 18). Focal adhe- sions are the specialized supramolecular assemblies that contain integrins and various inte- grin-associated signaling molecules and cytoskeletal proteins, thereby linking intracellular proteins to the extracellular matrices. Kuo, Han, Yates III, and Waterman present effec- tive protocols for isolating focal adhesion proteins and performing biochemical and pro- teomic analyses (Chapter 19). Talin constitutes the crucial intracellular protein that directly binds to the integrin cytoplasmic domain, thereby triggering integrin inside-out signaling. Bouaouina, Harburger, and Calderwood describe various methods used to investigate the roles of talin in the regulation of integrin activation (Chapter 20). At the leading edge of those cells migrating on the substrates, a cytoskeletal rearrangement occurs that is regu- lated by cascades of intracellular signaling events, all of which culminates in the formation of the characteristic membrane protrusion known as pseudopodium (or lamellipodium).
- 12. vii Preface Wang and Klemke detail a proteomics-based method for investigating signaling events, specifically phosphotyrosine proteins at the pseudopodium (Chapter 21). Part V (Chapters 22–26) covers experimental techniques to investigate integrin func- tions at organismal levels in a physiological context. Lowell and Mayadas begin Part V with an overview of integrin functions in vivo, which includes a comprehensive discussion of integrin knockout mice phenotypes observed during the developmental process, as well as under pathophysiological conditions (Chapter 22). Conditional gene targeting is a powerful technology that enables researchers to modify genes of interest in vivo only in specific tissue/cell-types or at a specific time-point during development. Yamamoto and Takeda describe a method for generating conditionally gene-targeted mice (Chapter 23). Analyzing how cells migrate to specific tissues is essential to the study of in vivo cell- adhesion molecule and chemo-attractant receptor functionality in these cells. De Calisto, Villablanca, Wang, Bono, Rosemblatt, and Mora first provide an overview of the mecha- nisms by which tissue-specific lymphocyte homing is regulated, and then present a proto- col to examine T-cell homing to the gut (Chapter 24). Proteomic analysis utilizing stable isotope labeling with amino acid in cell culture (SILAC) was originally utilized for cell biology studies in vitro. Zanivan, Krueger, and Mann discuss SILAC mice technology and its successful in vivo application for quantitative proteomic analysis of b1 integrin-deficient mice (Chapter 25). Dictyostelium discoideum amebae represent an excellent model organ- ism for studying the chemotactic responses of migrating cells. Cai, Huang, Devreotes, and Iijima detail the use of this model organism to elucidate the signaling machinery of chemotaxis (Chapter 26). Part VI (Chapters 27–30) showcases the most promising methods and technologies for the development of novel therapeutics and diagnostics. Foubert and Varner begin Part VI by providing a concise summary of the role integrins play in tumor angiogenesis and lymphangiogenesis, and then describe the methods used to study integrin functional- ity in these pathologies (Chapter 27). Radiopharmaceutics targeting integrins have been considered for tumor imaging. Dearling and Packard discuss a novel application, the use of b7 integrin-targeted radiopharmaceutics to image gut inflammation in a mouse model of inflammatory bowel disease (Chapter 28). Drug delivery is the major problem prevent- ing clinical realization of RNAi-based medicine. Ben-Arie, Kedmi, and Peer describe the application of integrin-targeted nanoparticles for leukocyte-directed siRNA delivery (Chapter 29). Drug candidates targeting integrins in patients often exhibit little or no cross-reactivity with rodent counter-parts, thereby making it difficult to perform preclini- cal studies. Kim, Kumar, and Shankar detail the generation of humanized mice harbor- ing human hematopoietic cells for the study of HIV infection, an approach with potential preclinical applications for validating other human integrin-targeted drug candidates in vivo (Chapter 30). As can be surmised here, the 30 chapters in this book cover many of the most impor- tant topics in the field of integrins and cell-adhesion molecules. I hope that this book will serve as a useful and valuable reference for both experts and nonexperts in the scientific community who wish to study cell-adhesion molecules. Finally, I would like to thank Dr. John Walker for the opportunity to edit this volume. I would also like to acknowledge all of the authors for their outstanding contributions to Integrins and Cell Adhesion Molecules: Methods and Protocols.
- 14. ix Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii Part I Basic Protocols for the Study of Integrin and Related Cell Adhesion Molecule Functionality In Vitro 1 Overview: Assays for Studying Integrin-Dependent Cell Adhesion . . . . . . . . . . . . 3 Alexandre Chigaev and Larry A. Sklar 2 Cell Adhesion Assays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Gabriele Weitz-Schmidt and Stéphanie Chreng 3 Real-Time Analysis of Integrin-Dependent Transendothelial Migration and Integrin-Independent Interstitial Motility of Leukocytes . . . . . . . . . . . . . . . . 31 Ziv Shulman and Ronen Alon 4 Lentiviral Gene Transfer Method to Study Integrin Function in T Lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Daliya Banerjee and Motomu Shimaoka 5 Surface Plasmon Resonance Biosensing in Studies of the Binding Between b2 Integrin I Domains and Their Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Thomas Vorup-Jensen 6 Cell-Free Ligand-Binding Assays for Integrin LFA-1 . . . . . . . . . . . . . . . . . . . . . . 73 Koichi Yuki Part II Structural Biology Approaches for Studying Integrins and Related Cell Adhesion Molecules 7 Overview: Structural Biology of Integrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Guanyuan Fu, Wei Wang, and Bing-Hao Luo 8 Protein Expression and Purification of Integrin I Domains and IgSF Ligands for Crystallography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Hongmin Zhang and Jia-huai Wang 9 Electron Microscopic Imaging of Integrin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Kenji Iwasaki 10 An NMR Method to Study Protein–Protein Interactions . . . . . . . . . . . . . . . . . . . 129 Noritaka Nishida and Ichio Shimada 11 Single-Molecule Methods to Study Cell Adhesion Molecules . . . . . . . . . . . . . . . . 139 Joonil Seog Part III Imaging for Investigating Cell Adhesion and Migration 12 Overview: Imaging in the Study of Integrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Christopher V. Carman
- 15. x Contents 13 Live Imaging of LFA-1-Dependent T-Cell Motility and Stop Signals . . . . . . . . . . 191 Andrew J. Wiemer, Sarah Wernimont, and Anna Huttenlocher 14 Monitoring Integrin Activation by Fluorescence Resonance Energy Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 Craig T. Lefort, Young-Min Hyun, and Minsoo Kim 15 High-Resolution Fluorescence Microscopy to Study Transendothelial Migration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 Christopher V. Carman 16 Multiphoton Intravital Microscopy to Study Lymphocyte Motility in Lymph Nodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Thomas T. Murooka and Thorsten R. Mempel Part IV Signaling Through Cell Adhesion Molecules 17 Overview of Integrin Signaling in the Immune System . . . . . . . . . . . . . . . . . . . . . 261 Tatsuo Kinashi 18 Rap1 and Integrin Inside-Out Signaling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 Koko Katagiri and Tatsuo Kinashi 19 Isolation of Focal Adhesion Proteins for Biochemical and Proteomic Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 Jean-Cheng Kuo, Xuemei Han, John R. Yates III, and Clare M. Waterman 20 Talin and Signaling Through Integrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325 Mohamed Bouaouina, David S. Harburger, and David A. Calderwood 21 Proteomics Method for Identification of Pseudopodium Phosphotyrosine Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 Yingchun Wang and Richard L. Klemke Part V Cell Adhesion and Migration at Organismal Levels in a Physiological Context 22 Overview: Studying Integrins In Vivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 Clifford A. Lowell and Tanya N. Mayadas 23 A Method for the Generation of Conditional Gene-Targeted Mice . . . . . . . . . . . . 399 Masahiro Yamamoto and Kiyoshi Takeda 24 T-Cell Homing to the Gut Mucosa: General Concepts and Methodological Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411 Jaime De Calisto, Eduardo J. Villablanca, Sen Wang, Maria R. Bono, Mario Rosemblatt, and J. Rodrigo Mora 25 In Vivo Quantitative Proteomics: The SILAC Mouse . . . . . . . . . . . . . . . . . . . . . . 435 Sara Zanivan, Marcus Krueger, and Matthias Mann 26 Analysis of Chemotaxis in Dictyostelium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 Huaqing Cai, Chuan-Hsiang Huang, Peter N. Devreotes, and Miho Iijima
- 16. xi Contents Part VI Methods and Technologies Towards Novel Therapeutics and Diagnostics Targeting Integrins 27 Integrins in Tumor Angiogenesis and Lymphangiogenesis . . . . . . . . . . . . . . . . . . 471 Philippe Foubert and Judith A. Varner 28 PET-Radioimmunodetection of Integrins: Imaging Acute Colitis Using a 64 Cu-Labeled Anti-b7 Integrin Antibody . . . . . . . . . . . . . . . . . . . . . . . . . 487 Jason L.J. Dearling and Alan B. Packard 29 Integrin-Targeted Nanoparticles for siRNA Delivery . . . . . . . . . . . . . . . . . . . . . . 497 Noa Ben-Arie, Ranit Kedmi, and Dan Peer 30 Humanized Mice for Studying Human Leukocyte Integrins In Vivo . . . . . . . . . . 509 Sang-Soo Kim, Priti Kumar, Chunting Ye, and Premlata Shankar Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523
- 18. xiii Contributors Ronen Alon • Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel Daliya Banerjee • Immune Disease Institute, Program in Cellular and Molecular Medicine at Children’s Hospital Boston, Boston, MA, USA; Department of Anesthesia, Harvard Medical School, Boston, MA, USA Noa Ben-Arie • Laboratory of Nanomedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel Maria R. Bono • Facultad de Ciencias, Universidad de Chile and Fundacion Ciencia para la Vida, Santiago, Chile Mohamed Bouaouina • Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, CT, USA Huaqing Cai • Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA David A. Calderwood • Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, CT, USA Christopher V. Carman • Center for Vascular Biology Research, Division of Molecular and Vascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Alexandre Chigaev • Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA Stéphanie Chreng • Novartis Institutes for BioMedical Research, Basel, Switzerland Jaime De Calisto • Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Jason L. J. Dearling • Division of Nuclear Medicine, Department of Radiology, Children’s Hospital Boston, Boston, MA, USA; Harvard Medical School, Boston, MA, USA Peter N. Devreotes • Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA Phillipe Foubert • Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA, USA Guanyuan Fu • Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA Xuemei Han • Cell Biology, Scripps Research Institute, La Jolla, CA, USA
- 19. xiv Contributors DAVID S. HARBURGER s Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, CT, USA CHUAN-HSIANG HUANG s Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA ANNA HUTTENLOCHER s Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA; Department of Pediatrics, University of Wisconsin, Madison, WI, USA YOUNG-MIN HYUN s Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA MIHO IIJIMA s Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA KENJI IWASAKI s Research Center for Structural and Functional Proteomics, Institute for Protein Research, Osaka University, Suita, Osaka, Japan KOKO KATAGIRI s Department of Life Science, School of Science and Technology, Kansei Gakuin University, Hyogo, Japan RANIT KEDMI s Laboratory of Nanomedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel MINSOO KIM s Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA SANG-SOO KIM s Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Reservoir Road NW, Washington, DC, USA TATSUO KINASHI s Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Osaka, Japan RICHARD L. KLEMKE s Department of Pathology, University of California, San Diego, Basic Science, La Jolla, CA, USA MARCUS KRUEGER s Department of Cardiac Development and Remodeling, Max-Planck-Institute of Heart and Lung Research, Bad Nauheim, Germany PRITI KUMAR s Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA JEAN-CHEUNG KUO s Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, Bethesda, MD, USA CRAIG T. LEFORT s Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA CLIFFORD A. LOWELL s Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA BING-HAO LUO s Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA MATTHIAS MANN s Department of Proteomics and Signal Transduction, Max-Planck-Institute of Heart and Lung Research, Bad Nauheim, Germany
- 20. xv Contributors Tanya N. Mayadas • Department of Pathology, Center of Excellence in Vascular Biology, Brigham and Women’s Hospital Harvard Medical School, Boston, MA, USA Thorsten R. Mempel • Center for Immunology and Inflammatory Diseases and Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA J. Rodrigo Mora • Gastrointestinal Unit, Massachusetts General Hospital, GRJ-815, Boston, MA, USA Thomas T. Murooka • Center for Immunology and Inflammatory Diseases and Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Noritaka Nishida • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan Alan B. Packard • Division of Nuclear Medicine, Department of Radiology, Children’s Hospital Boston, Boston, MA, USA; Harvard Medical School, Boston, MA, USA Dan Peer • Laboratory of Nanomedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel Mario Rosemblatt • Facultad de Ciencias, Universidad de Chile; Facultad de Ciencias Biologicas, Universidad Andres Bello and Foundation Ciencia para la Vida, Santiago, Chile Joonil Seog • Department of Materials Science and Engineering, Fischell Bioengineering Department, University of Maryland, College Park, MD, USA Premlata Shankar • Department of Biomedical Sciences, Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA Ichio Shimada • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan; Japan Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Aomi, Koto-ku, Tokyo, Japan Motomu Shimaoka • Immune Disease Institute, Program in Cellular and Molecular Medicine at Children’s Hospital Boston, Department of Anesthesia, Harvard Medical School, Boston, MA, USA; Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu-City, Mie, JAPAN Ziv Shulman • Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel Larry A. Sklar • Department of Pathology and Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA Kiyoshi Takeda • Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan Laboratory of Mucosal Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan ;
- 21. xvi Contributors Judith A. Varner • Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA, USA Eduardo J. Villablanca • Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Thomas Vorup-Jensen • Biophysical Immunology Laboratory, Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus C, Denmark Jia-huai Wang • Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Sen Wang • Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Wei Wang • Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA Yingchun Wang • Key Laboratory of Molecular Development Biology, Insitute of Genetics and Development Bilogy, Chinese Academy of Sciences, Beijing, China Clare M. Waterman • Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, Bethesda, MD, USA Gabriele Weitz-Schmidt • Novartis Institutes for BioMedical Research, Basel, Switzerland; University Basel, PharmaCenter, Basel, Switzerland Sarah Wernimont • Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI, USA Andrew J. Wiemer • Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA Masahiro Yamamoto • Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Laboratory of Mucosal Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan John R. Yates III • Cell Biology, Scripps Research Institute, La Jolla, CA, USA Chunting Ye • Department of Biomedical Sciences, Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Tx, USA Koichi Yuki • Department of Anesthesiology, Perioperative and Pain Medicine, Children’s Hospital Boston, Boston, MA, USA; Immune Disease Institute, Boston, MA, USA; Department of Anaesthesia, Harvard Medical School, Boston, MA, USA Sara Zanivan • Vascular Proteomics Group,Beatson Institute for Cancer Research, Glasgow, United Kingdom Hongmin Zhang • Department of Physiology, The University of Hong Kong, Hong Kong, SAR, China
- 22. Part I Basic Protocols for the Study of Integrin and Related Cell Adhesion Molecule Functionality In Vitro
- 24. 3 Motomu Shimaoka (ed.), Integrin and Cell Adhesion Molecules: Methods and Protocols, Methods in Molecular Biology, vol. 757, DOI 10.1007/978-1-61779-166-6_1, © Springer Science+Business Media, LLC 2011 Chapter 1 Overview: Assays for Studying Integrin-Dependent Cell Adhesion Alexandre Chigaev and Larry A. Sklar Abstract Interaction of the integrin receptors with ligands determines the molecular basis of integrin-dependent cell adhesion. Integrin ligands are typically large proteins with relatively low binding affinities. This makes direct ligand-binding kinetic measurements somewhat difficult. Here we examine several real-time meth- ods, aimed to overcome these experimental limitations and to distinguish the regulation of integrin conformation and affinity. This chapter includes: the use of a small ligand-mimetic probe for studies of inside-out regulation of integrin affinity and unbending, real-time cell aggregation and disaggregation kinetics to probe integrin conformational states and the number of integrin–ligand bonds, as well as the real-time monitoring of ligand-induced epitopes under signaling through G-protein-coupled receptors, and others. Experimental data obtained using these novel methods are summarized in terms of the cur- rent model of integrin activation. Key words: Ligand–receptor interaction, Ligand mimetic, Real-time kinetics, Cells adhesion, Inside-out signal, Monoclonal antibodies, Quantitative approaches Understanding how cell adhesion and migration is regulated is essential for describing embryonic development, tissue repair, hemostasis, inflammation, cell mobilization, and metastasis. The ability to rapidly and reversibly modulate cellular adhesive pro perties serves as the basis for multiple biological functions of mul- ticellular organisms. Several adhesion molecules regulate cell adhesion through de novo expression, rapid upregulation by the means of exocytosis, downregulation through proteolysis, shed- ding, and other mechanisms that can alter the number of mole- cules on the cell surface. Methods for studying these molecules 1. Introduction
- 25. 4 A. Chigaev and L.A. Sklar are beyond the scope of this chapter. We focus here on integrins, a unique class of adhesion molecules that can rapidly change cell adhesion through a conformational change and/or clustering, without altering molecule expression. Our current understanding of integrin conformational reg- ulation implies the potential existence of multiple conforma- tional states, with different binding affinities for their ligands, different degrees of unbending (extension), and different posi- tioning of integrin domains (hybrid domain in particular). These states are expected to contribute to the lifetime of the ligand– receptor bond, and the efficiency of the bond formation. Such a model allows us to describe how an integrin such as VLA-4 can be responsible for very diverse cellular behaviors, such as a nonadhesive state, as well as rolling, cell arrest, and firm adhe- sion (1). The recent discovery that G-protein-coupled receptors can provide a negative (deactivating) signal, which results in cell deadhesion, adds to the number of possible conformational states and highlights the complexity of integrin conformational regulation (2). In this chapter, we review basic methods that led to the current model of integrin activation and focus on basic techniques that are currently used in our and other laboratories to study integrin- dependent cell adhesion. Because of the limited space we will primarily focus on unique assays specifically developed for integrin studies in our laboratory. We apologize to the others whose studies contributed to the current understanding of integrin regulation and were not cited because of the lack of space. Interaction of the integrin receptors with ligands determines the molecular basis of integrin-dependent cell adhesion. Methods that allow monitoring of these ligand–receptor interactions in real-time on living cells under physiologically relevant signaling conditions would represent a desirable “gold standard” for these types of studies. In the best case scenario a scientist should be able to purify cells of interest, add labeled ligand, and monitor binding of the probe in real time after activation/deactivation through other types of receptors (“inside-out” or “outside-in” signal). Unfortunately, soluble integrin ligands are large proteins that have relatively low binding affinities. Therefore, direct kinetic measure- ments of natural integrin ligand binding are technically difficult. One of the solutions to this problem is the development of small molecule probes that exhibit higher binding affinities and, at the same time, reflect the binding of the natural ligand. 2. Small Molecules as Tools for Integrin Studies
- 26. 5 1 Overview: Assays for Studying Integrin-Dependent Cell Adhesion These probes can be used as reporters of the affinity state of the integrin-binding pocket, as well as in other applications (see below). Fluorescently labeled molecules of this type can be used in a conventional flow cytometer to make homogeneous real-time measurements of ligand–receptor interactions (3, 4). Drug-like small molecules also appear to be good candidates for these assays. Integrins represent an attractive target for treatment of sev- eral diseases. Therefore, a number of drug-like small molecules (direct and allosteric integrin antagonists) have been developed by several pharmaceutical companies (5). Fluorescent antago- nists for GPIIb/IIIa (RGD peptidomimetics) were described and used in a flow cytometer by Dr. Bednar et al. from Merck Research Labs (4). The binding of fluorescent LFA-1 antagonists has been described by Dr. Keating et al. from Genentech, Inc. (6). We took advantage of the published structure of LDV-based com- petitive antagonists developed by Biogen Idec Inc. (BIO1211) (7, 8), and created a fluorescent probe that mimics binding of a natural VLA-4 (a4b1-integrin) ligand (9). This probe has been used for determination of rapid affinity changes of the integrin ligand-binding pocket in real time in our laboratory and others (9, 10). The assay is performed directly in a tube attached to a flow cytometer and cells are continuously sampled for periods up to several tens of minutes. For a short period of time the tube is removed from the cytometer and a signaling molecule of interest is added. Because the fluorescent probe is added at a concentra- tion sufficient to occupy only high-affinity VLA-4 sites, addi- tional binding of the probe is observed in response to an affinity change. The presence of the affinity change can be verified using dissociation rate analysis, where a large excess of the unlabelled competitor is added to prevent rebinding of the fluorescent probe. A strong correlation between dissociation rates for the probe and natural ligand, as well as cellular dissociation rates has been observed for the case of multiple affinity states (11, 12). The same fluorescent probe can be used to assess integrin unbending (Fig. 1). The ability to independently measure the affinity state of the ligand-binding pocket and molecular unbend- ing permitted us to study the regulation of these two processes through “inside-out” signaling. Surprisingly, this resulted in the observation that affinity and unbending are regulated by two independent signaling pathways (1). According to these types of measurements“inside-out”signalingthroughdifferentG-protein- coupled receptors results in a plethora of conformational states, at a minimum the four combinations of high and low affinity with independently regulated bent and unbent states (2). Thus, the idea that a single integrin molecule can adopt states suitable for rolling (extended and low affinity of the binding pocket), arrest (high affinity), and nonadhesive (low affinity bent with hidden
- 27. 6 A. Chigaev and L.A. Sklar binding pocket) may be realistic for non I-domain-containing integrins (such as VLA-4) (13). For integrins with an inserted domain (such as LFA-1), the situation is more complicated. The development of similar fluorescent ligand-mimicking probes for other integrins appears to be very beneficial. Small molecule probes with appropriate affinity (in the nM range) can be used for detecting affinity changes and unbending in real-time on live cells after activation and/or deactivation through signal- ing receptors. However, only competitive antagonists, which mimic the binding of a natural ligand, can be used for the detec- tion of the affinity change of the ligand-binding pocket. We have also used a fluorescent allosteric antagonist of LFA-1 (fluorescent derivative of BIRT-377) to probe vertical extension upon activa- tion in a FRET-based assay analogous to Fig. 1 (14). Only the reducing agent DTT caused a large FRET signal change, in a manner analogous to DTT-induced extension of VLA-4 (15). The absence of a large conformational change was explained by the fact that BIRT was shown to stabilize the inactive (bent) con- formation of LFA-1 (14). Nevertheless, the question remains open why b1-, and b3-integrin-specific small molecules are pre- dominantly competitive antagonists, while the majority of b2-integrin antagonists are allosteric (at least for LFA-1) (5). Fig. 1. Schematic depicting the FRET assay for assessing VLA-4 conformational unbending (modified from (1)). Energy transfer between VLA-4 head groups and lipid probes incor- porated into the plasma membrane provides a way of studying integrin conformational unbending.The LDV-FITC probe that specifically binds to the head group of VLA-4 is used as a fluorescent donor at a high enough concentration to saturate all low-affinity resting binding sites. A change in VLA-4 affinity would not affect probe binding. Octadecyl rhod- amine B (R18), a lipophilic probe, inserts into the membrane as an acceptor. Upon activa- tion, VLA-4 assumes an unbent (upright) conformation. rC1 and rC2 are the distances of closest approach before and after molecular unbending. Changes in the fluorescence of the donor were measured on live cells in real time at 37°C by flow cytometry.
- 28. 7 1 Overview: Assays for Studying Integrin-Dependent Cell Adhesion Rapid kinetic measurements of natural integrin ligands binding and other protein–protein interaction are possible with the use of a rapid-mix flow cytometer (16–18). In a conventional flow cytometer several seconds are required for the delivery of a sample from a test tube to the flow chamber. Modern automated rapid- mix devices allow mixing and delivery under a second using microliter volume of samples (55–600 ms, 35–45 ml aliquots) (16, 18). We used a rapid-mix flow cytometer to determine the dissociation rate of soluble fluorescently labeled recombinant human VCAM from a rapidly dissociating intermediate affinity state of VLA-4 integrin. However, a direct measurement of the VCAM dissociation rate for resting VLA-4 (without activation and with physiological concentrations of divalent cations) using this technique is still elusive (12). Nonetheless, the single mole- cule dissociation rates appear to provide insight into the duration of cell adhesion as described below. Single bond life-times have also been evaluated with the bio- force probe (19). When these measurements are extrapolated to 0 force, the bioforce probe and flow cytometry measurements give comparable results (Evan Evans, unpublished data). Another powerful method for studying real-time integrin activation and cell adhesion is the cell-suspension adhesion assay. Two types of cells, one population expressing the integrin of interest along with activating or inhibiting pathway receptors (G-protein-coupled receptor) and the other cell population expressing an integrin ligand, can be stained with two fluorescent dyes (e.g., green and red). For the case of homotypic aggregation, such as neutrophil aggregation, a single color stain is sufficient (20). After cells are mixed in a tube maintained at 37°C with constant stirring, they are continuously sampled over several tens of minutes. Aggregates, which are formed over a period of time, are detected as double-positive (green and red co-fluorescent) events. Because flow cytometers also detect single cells (only green or red events), it is possible to follow cell aggrega- tion in real time by evaluating the aggregates or depletion of “singlets.” This allows eliminating the effect of multicellular aggregates that present in the double-positive gate (11). Using this methodology it is possible to observe GPCR- dependent activation of integrin-dependent cell adhesion (“inside-out” activation), as well as rapid deactivation and cell disaggregation (1, 2, 20) (Fig. 2). Moreover, it was possible to 3. Single Bond Life-Times 4. Real-Time Aggregation and Disaggregation Kinetics
- 29. 8 A. Chigaev and L.A. Sklar establish a relationship between cellular disaggregation rates and ligand dissociation rates for different affinity states. Quantitative analysis of molecular and cellular dissociation rates revealed that only a small number of VLA-4-VCAM-1 bonds (~1.5 on aver- age) was sufficient to hold together cellular aggregates (11). This method can be also adopted to study cell aggregation and disaggregation under force. We and others have used devices which create defined shear in cone and plate as well as parallel-plate conditions (i.e., Ravenfield model EM Shear Generator (Ravenfield Designs Ltd., Heywood, UK) (12, 21). As expected, shear stress had a significant effect on cellular disaggregation rates (12). The work of Simon et al. showed how the contributions of L-selectin with PSGL and b2-integrin with ICAM-1 worked together under shear in neutrophil aggre- gation (20, 22). The method can be also used to determine cellular associa- tion rates (analogous to the “forward kinetics” for the ligand binding). Based on our measurements of integrin molecule exten- sion (using a FRET-based assay, see below), we postulated that molecular extension could facilitate integrin ligand recruitment because of the better exposure of the integrin ligand-binding pocket. We established experimental conditions to enhance inte- grin extension (determined using a FRET-based assay) while maintaining the affinity state of the ligand-binding pocket (deter- mined in a ligand dissociation assay). We found that the initial rate of cell aggregation was dramatically elevated for the case of “extended” integrins (see Fig. 9 in (1)). Fig. 2. Changes in cell adhesion between formyl peptide transfected U937 cell and VCAM-1-transfected B78H1 cells at resting state and in response to receptor stimula- tion (modified from (1)).Addition of fMLFF (formyl peptide) induces cell aggregation.This results in U937 singlets depletion. PLC inhibitor U-73122 has the opposite effect.
- 30. Another Random Document on Scribd Without Any Related Topics
- 31. SENSATION. HEDIO. alone is the source of salvation, and he is so every where,—these were the two truths which he learned at Einsidlen, and they became fundamental articles in his creed. The serious impression produced on his soul soon manifested itself externally. Struck with the many prevailing evils, he resolved to oppose them boldly. Not hesitating between his conscience and his interest, he stood up openly, and, in plain and energetic terms, attacked the superstition of the surrounding crowds: Think not, said he from the pulpit, that God is in this temple more than in any other part of his creation. Whatever be the country in which you dwell, God encompasses you, and hears you as well as in our Lady of Einsidlen. Can useless works, long pilgrimages, offerings, images, the invocation of the Virgin, or the saints, obtain the grace of God?... What avails the multitude of words in which we embody our prayers? What avails a glossy hood— a head well shaven—a long robe with its neat folds, and mules caparisoned with gold? God looks to the heart, but our heart is alienated from God.[670] But Zuinglius wished to do more than lift his voice against superstition. He wished to satisfy that eager longing for reconciliation with God, felt by many of the pilgrims who had flocked to the chapel of our Lady of Einsidlen. Christ, cried he, like a John Baptist in this new wilderness of Judea, Christ, who was once offered on the cross, is the expiatory victim, who, even through eternity, makes satisfaction for the sins of all believers.[671] Thus Zuinglius advanced. The day when this bold sermon was heard in the most venerated sanctuary of Switzerland, the standard prepared against Rome began to be more distinctly displayed on its mountain heights, and there was, so to speak, a heaving of reform reaching even to their deepest foundations. In fact, universal astonishment seized the multitude on hearing the discourse of the eloquent priest. Some walked off in horror; others hesitated between the faith of their fathers and the doctrine fitted to secure their peace, while several came to Jesus Christ who was thus
- 32. ZUINGLIUS AND THE LEGATES. preached to them, and finding rest to their souls, took back the tapers which they had intended to present to the Virgin. A crowd of pilgrims returned to their homes, announcing every where what they had heard at Einsidlen. Christ ALONE saves, and saves EVERYWHERE. Bands, astonished at what they heard, stopped short without finishing their pilgrimage. The worshippers of Mary diminished from day to day. Their offerings formed almost the whole income of Zuinglius and Geroldsek; but the intrepid witness of the truth felt happy to be impoverished in order that souls might be spiritually enriched. During the feast of Pentecost, in the year 1518, among the numerous hearers of Zuinglius, was a learned man of meek temper and active charity, named Gaspard Hedio, doctor of theology at Bâle. Zuinglius preached on the cure of the paralytic, (Luke, v,) where our Saviour declares, The Son of Man hath power upon earth to forgive sins, words well fitted to strike the crowd assembled in the Church of the Virgin. The preacher roused, enraptured, and inflamed his audience, especially the doctor from Bâle.[672] A long time after, Hedio expressed his high admiration; How beautiful, said he, this discourse, how profound, weighty, complete, penetrating, and evangelical; how much it reminds one of the ενεργεια (energy) of the ancient doctors.[673] From that moment Hedio admired and loved Zuinglius.[674] He would fain have gone to him, and opened his heart; he wandered around the abbey but durst not approach, kept back, as he expresses it, by a superstitious timidity. He again mounted his horse and slowly retired from our Lady, ever and again turning his head to the spot which contained so great a treasure, and feeling in his heart the keenest regret.[675] Thus Zuinglius preached; less forcibly, no doubt, than Luther, but with more moderation, and not less success. He did nothing precipitately, and did not come so violently into collision with men's minds as the Saxon Reformer; he expected every thing from the power of truth. He
- 33. displayed the same wisdom in his relations with the heads of the Church. Far from immediately declaring himself their enemy, he long remained their friend. They were exceedingly indulgent to him, not only because of his learning and talents, (Luther had the same claims to the regard of the bishops of Mentz and Brandenburg,) but especially because of his attachment to the pope's political party, and the influence possessed by such a man as Zuinglius in a republican state. In fact, several cantons, disgusted with the service of the pope, were disposed to break with him. But the legates flattered themselves they might retain several of them by gaining Zuinglius, as they gained Erasmus, with pensions and honours. At this time the legates, Ennius and Pucci, went frequently to Einsidlen, where from its proximity to the democratic cantons, it was more easy to carry on negotiations with them. But Zuinglius, far from sacrificing the truth to the demands and offers of Rome, omitted no opportunity of defending the gospel. The famous Schinner, who had then some disturbance in his diocese, passed some time at Einsidlen. The whole papacy, said Zuinglius one day, rests on a bad foundation. [676] Put your hand to the work, remove errors and abuses, or you will see the whole edifice crumble to pieces with fearful uproar.[677] He spoke with the same frankness to legate Pucci. Four times did he return to the charge. With the help of God, said he to him, I will continue to preach the gospel, and this preaching will shake Rome. Then he pointed out to him what was necessary to save the Church. Pucci promised every thing, but did nothing. Zuinglius declared that he renounced the pension from the pope. The legate entreated him to retain it; and Zuinglius, who at that time had no thought of placing himself in open hostility to the head of the Church, consented for three years to receive it. But think not, added he, that for the love of money I retrench a single syllable of the truth. [678] Pucci, alarmed, made the Reformer be appointed chaplain acolyte to the pope. It was an avenue to new honours. Rome thought to frighten Luther by sentences of condemnation, and to
- 34. THE BISHOP OF CONSTANCE. SAMSON AND INDULGENCES. win Zuinglius by favours—darting her excommunications at the one, and displaying her gold and magnificence to the other. She thus endeavoured, by two different methods, to attain the same end, and silence the bold lips which dared, in spite of the pope, to proclaim the Word of God in Germany and Switzerland. The latter method was the more skilful, but neither of them succeeded. The enfranchised souls of the preachers of truth were equally inaccessible to menace and favour. Another Swiss prelate, Hugo of Landenberg, bishop of Constance, at this time gave some hopes to Zuinglius. He ordered a general visitation of the churches. But Landenberg, a man of no character, allowed himself to be led alternately by Faber, his vicar, and by an abandoned female, from whose sway he was unable to escape. He occasionally appeared to honour the gospel, and yet any one who preached it boldly was in his eyes only a disturber. He was one of those men too common in the Church, who, though loving truth better than error, have more indulgence for error than for truth, and often end by turning against those with whom they ought to make common cause. Zuinglius applied to him, but in vain. He was to have the same experience which Luther had; to be convinced that it was useless to invoke the heads of the Church, and that the only method of restoring Christianity was to act as a faithful teacher of the Word of God. An opportunity of doing so soon occurred. In August, 1518, a Franciscan monk was seen travelling on the heights of St. Gothard, in those lofty passes which have been laboriously cut across the steep rocks separating Switzerland from Italy. Having come forth from an Italian convent, he was the bearer of papal indulgences which he was commissioned to sell to the good Christians of the Helvetic league. Brilliant success, obtained under two preceding popes, had signalised his exertions in this shameful traffic. Companions, intended to puff off the merchandise which he was going to sell, were accompanying him across mountains of snow
- 35. STAPFER AND ZUINGLIUS. and ice coeval with the world. This avaricious band, in appearance miserable enough, and not unlike a band of adventurers roaming for plunder, walked in silence, amid the noise of the foaming torrents which give rise to the Rhine, the Reuss, the Aar, the Rhone, the Tessino, and other rivers, meditating how they were to plunder the simple population of Helvetia. Samson (this was the Franciscan's name) and his company first arrived in Uri, and there commenced their traffic. They had soon done with these poor peasants, and passed into the canton of Schwitz. Here Zuinglius was, and here the combat between these two servants of two very different masters was to take place. I can pardon all sins, said the Italian monk, the Tezel of Switzerland. Heaven and hell are subject to my power, and I sell the merits of Jesus Christ to whoever will purchase them, by paying in cash for an indulgence. Zuinglius heard of these discourses, and his zeal was inflamed. He preached powerfully against them. Jesus Christ, the Son of God, said he, thus speaks, 'Come unto ME, all ye that labour and are heavy laden, and I will give you rest.' Is it not then audacious folly and insensate temerity to say on the contrary, Purchase letters of indulgence! run to Rome! give to the monks! sacrifice to the priests! If you do these things I will absolve you from your sins![679] Jesus Christ is the only offering; Jesus Christ is the only sacrifice; Jesus Christ is the only way.[680] Every body at Schwitz began to call Samson rogue and cheat. He took the road to Zug, and for this time the two champions failed to meet. Scarcely had Samson left Schwitz when a citizen of this canton, named Stapfer, a man of distinguished talent, and afterward secretary of state, was with his family reduced to great distress. Alas, said he, when applying in agony to Zuinglius, I know not how to satisfy my own hunger and the hunger of my poor children.
- 36. [681] Zuinglius knew to give where Rome knew to take; he was as ready to practise good works, as to combat those who taught that they were the means of obtaining salvation. He daily gave liberally to Stapfer.[682] It is God, said he, anxious not to take any glory to himself, It is God who begets charity in the believer, and gives him at once the thought, the resolution, and the work itself. Whatever good a righteous man does it is God who does it by his own power. [683] Stapfer remained attached to him through life; and, four years after, when he had become secretary of state, and felt wants of a higher kind, he turned towards Zuinglius, and said to him with noble candour, Since you provided for my temporal wants, how much more may I now expect from you wherewith to appease the hunger of my soul! The friends of Zuinglius increased. Not only at Glaris, Bâle, and Schwitz, did he find men of like spirit with himself; in Uri there was the secretary of state, Schmidt; at Zug, Colin Müller and Werner Steiner, his old companions in arms at Marignan: at Lucerne, Xylotect and Kilchmeyer; Wittembach at Berne, and many others in many other places. But the curate of Einsidlen had no more devoted friend than Oswald Myconius. Oswald had quitted Bâle in 1516, to take charge of the cathedral school at Zurich. In this town there were no learned men, and no schools of learning. Oswald laboured along with some well-disposed individuals, among others, Utinger, notary to the pope, to raise the Zurich population out of ignorance and initiate them in ancient literature. At the same time he defended the immutable truth of the Holy Scriptures, and declared that if the pope or emperor gave commands contrary to the gospel, obedience was due to God alone, who is above both emperor and pope.
- 38. CHAP. VI. Zurich—The College of Canons—Election to the Cathedral—Fable —Accusations—Confession of Zuinglius—The Designs of God Unfolded—Farewell to Einsidlen—Arrival at Zurich— Courageous Declaration of Zuinglius—First Sermons— Effects—Opposition—Character of Zuinglius—Taste for Music—Arrangement of the Day—Circulation by Hawkers. Seven centuries had elapsed since Charlemagne had attached a college of canons to this cathedral, over whose school Oswald Myconius then presided. These canons having degenerated from their first institution, and desiring in their benefices to enjoy the sweets of indolence, elected a priest to preach and take the cure of souls. This situation having become vacant some time after Oswald's arrival, he immediately thought of his friend. What a prize it would be for Zurich! Zuinglius' appearance was prepossessing. He was a handsome man,[684] of graceful address, and pleasing manners. His eloquence had already given him celebrity, while the lustre of his genius made him conspicuous among all the confederates. Myconius spoke of him to the provost of the chapter, Felix Frey, (who from the appearance and talents of Zuinglius was already prepossessed in his favour,)[685] to Utinger, an old man who was held in high respect, and to canon Hoffman, a man of an upright open disposition, who, having long preached against foreign service, was favourably inclined to Ulric. Other Zurichers had, on different occasions, heard Zuinglius at Einsidlen, and had returned full of admiration. The election of preacher to the cathedral soon set all the inhabitants of Zurich in motion. Different parties were formed. Several laboured night and day for the election of the eloquent preacher of Our Lady of the Eremites.[686] Myconius having informed his friend —Wednesday next, replied Zuinglius, I will come and dine at
- 39. CHARGES AGAINST ZUINGLIUS. Zurich, and talk over matters. He accordingly arrived. A canon to whom he was paying a visit said to him, Could you come among us to preach the word of God? I could, replied he; but will not come unless I am called. He then returned to his abbey. This visit spread alarm in the camp of his enemies. Several priests were urged to apply for the vacancy. A Suabian, named Laurent Fable, even preached as a candidate, and the rumour went that he was elected. It is then quite true, said Zuinglius, on learning it, that a prophet has no honour in his own country, since a Suabian is preferred to a Swiss. I know what value to set on popular applause. [687] Zuinglius immediately after received a letter from the secretary of Cardinal Schinner, informing him, that the election had not taken place. But the false news which he had at first received nettled the curate of Einsidlen. Knowing that a person so unworthy as this Fable aspired to the place, he was more desirous to obtain it for himself, and wrote about it to Myconius, who next day replied, Fable will always continue fable: my masters have learned that he is already the father of six boys, and possesses I know not how many benefices.[688] The enemies of Zuinglius did not abandon their opposition. All, it is true, agreed in extolling his learning to the skies;[689] but said some, He is too fond of music; others, He loves the world and pleasure; others again, In early life he was too closely connected with giddy companions. There was even one individual who charged him with an instance of seduction. Zuinglius was not without blemish. Though superior to the ecclesiastics of his time he more than once, in the first years of his ministry, gave way to youthful propensities. It is difficult to estimate the influence of an impure atmosphere on those who live in it. There were in the papacy certain established irregularities, allowed and sanctioned as conformable to the laws of nature. A saying of Æneas Sylvius, afterwards pope under the name of Pius II, gives an idea of the sad state of public morals at this
- 40. CONFESSION BY ZUINGLIUS. period. We give it in a note.[690] Disorder had become the rule, order the exception. Oswald displayed the greatest activity in favour of his friend. He exerted all his powers in defending him, and happily succeeded.[691] He went to burgomaster Roust, to Hoffman, Frey, and Utinger. He praised Zuinglius for his probity, honesty, and purity, and confirmed the Zurichers in the favourable opinion which they had of the curate of Einsidlen. Little credit was given to the speeches of his adversaries. The most influential persons said, that Zuinglius should be preacher at Zurich. The canons said so also, but in a whisper. Hope, wrote Oswald to him with a full heart, for I hope. At the same time he told him of the accusations of his enemies. Although Zuinglius was not yet become altogether a new man, he belonged to the class of those whose conscience is awakened, and who may fall into sin, but never without a struggle, or without remorse. It had often been his resolution to stand alone in the midst of the world, and maintain a life of holiness. But when he saw himself accused, he did not pretend to boast that he was without sin. Writing to canon Utinger, he said, Having nobody to go along with me in the resolutions which I had formed, several even of those about me, being offended at them, alas! I fell, and like the dog of whom St. Peter speaks, (2 Ep. ii, 22,) returned to my vomit.[692] Ah! God knows with what shame and anguish I have torn up these faults from the depths of my heart, and laid them before Almighty God, to whom, however, I would be less afraid to confess my misery than to mortal man.[693] But while Zuinglius confessed himself to be a sinner, he, at the same time vindicated himself from the most offensive charges which were brought against him. He declared that he had ever abhorred the idea of invading the sanctity of married life, or seducing innocence,[694]— vices at that time but too common, or the truth of this, says he, I appeal to all with whom I have lived.[695]
- 41. ARRIVAL AT ZURICH. The election took place on the 11th December, and out of the twenty-four votes which were given, Zuinglius had seventeen. It was time that the Reformation should begin in Switzerland. The chosen instrument which Divine Providence had been preparing during three years in the retreat of Einsidlen, was ready and must now be translated elsewhere. God, who had chosen the new university of Wittemberg, situated in the heart of Germany, and under the protection of the wisest of princes, to call Luther thither, made choice in Switzerland of the city of Zurich, regarded as the head of the confederation, there to station Zuinglius, and to bring him into contact not only with one of the most intelligent, simple, resolute, and intrepid communities of Switzerland, but also with all the cantons which are grouped around this ancient and powerful state. The hand which had taken hold of a young shepherd of Sentis, and led him to the school of Wesen, now brought him forward, powerful in word and in deed, in the face of all, to regenerate his countrymen. Zurich was about to become a focus of light to Switzerland. The day which announced the election of Zuinglius was to Einsidlen a day at once of joy and grief. The circle which had been formed there was about to be broken up by the withdrawal of its most valuable member, and who could say whether superstition was not going again to take possession of this ancient place of pilgrimage?... The council of state in Schwitz conveyed the expression of its sentiments to Ulric by designating him as reverend, learned, most gracious master, and good friend.[696] At least do you yourself give us a successor worthy of you, said Geroldsek in despair to Zuinglius. I have got for you, replied he, a little lion, simple and wise; a man initiated in the mysteries of sacred science. Let me have him, immediately rejoined the administrator. It was Leo Juda, at once the gentle and intrepid friend with whom Zuinglius had been so intimate at Bâle. Leo accepted the call which brought him near his dear Ulric. Ulric took farewell of his friends, quitted the solitude of Einsidlen, and arrived at that delightful spot where, smiling and instinct with life, rises the town of Zurich, surrounded by its amphitheatre of vine-clad
- 42. INSTRUCTIONS OF THE CHAPTER. ZUINGLIUS' DECLARATION. hills, enamelled with meadows and orchards, crowned with forests, and overtopped by the lofty peaks of the Albis. Zurich, the centre of the political interests of Switzerland, where the most influential persons in the nation frequently assembled, was the place best fitted to act upon the whole country, and shed the seeds of truth over all its cantons. Accordingly, the friends of letters and the Bible hailed the appointment of Zuinglius with acclamation. At Paris, in particular, the Swiss students, who were there in great numbers, were enraptured with the news.[697] But if Zuinglius had the prospect of a great victory at Zurich, he had also the prospect of a severe contest. Glarean wrote him from Paris, I foresee that your learning will stir up great enmity;[698] but be of good courage, and you will, like Hercules, subdue monsters.[699] On the 27th December, 1518, Zuinglius arrived at Zurich, and took up his quarters at the hotel of Einsidlen. He received a cordial and honourable welcome. The chapter immediately met to receive him, and invited him to take his seat in the midst of them. Felix Frey presided; the canons, friendly or hostile to Zuinglius, sat indiscriminately around their provost. There was considerable excitement in the meeting; every one felt, perhaps without distinctly acknowledging it to himself, how serious the commencement of this ministry was likely to prove. Some apprehension being entertained of the innovating spirit of the young priest, it was agreed to set before him the most important duties of his office. You will use your utmost endeavour, he was gravely told, to secure payment of the revenues of the chapter, without neglecting the least of them. You will exhort the faithful both from the pulpit and in the confessional, to pay the first fruits and tithes, and to show by their offerings that they love the Church. You will make it your business to increase the revenues which are derived from the sick, from sacrifices, and generally from every ecclesiastical act. The chapter added, As to the administration of the sacraments, preaching, and personal presence, amid the flock, these
- 43. ZUINGLIUS' FIRST SERMONS AT ZURICH. too are duties of the priest. However, in these different respects, and particularly in regard to preaching, you may supply your place by a vicar. You should administer the sacraments only to persons of distinction, and after being requested. You are expressly forbidden to do it to all persons indiscriminately.[700] Strange rule to be given to Zuinglius! Money, money, still money!... Was it then for this that Christ established his ministry? Still prudence tempers his zeal; he knows that we cannot all at once deposit the seed in the ground, see the growth of the tree, and gather its fruit. Zuinglius, therefore, without explaining his views on what was enjoined him, humbly expressed his gratitude for the honourable appointment which he had received, and stated what he calculated on being able to do. The life of Jesus, said he, has been too long hidden from the people. I will preach on the whole gospel of St. Matthew, chapter by chapter, following the mind of the Holy Spirit, drawing only at the well-springs of Scripture,[701] digging deep into it, and seeking the understanding of it by persevering fervent prayer.[702] I will consecrate my ministry to the glory of God; the praise of His only Son; the real salvation of souls, and their instruction in the true faith.[703] This new language made a deep impression on the chapter. Some expressed joy, but the majority openly disapproved.[704] This mode of preaching is an innovation, exclaimed they, this innovation will soon lead to others, and where is it to stop? Canon Hoffman in particular thought it his duty to prevent the fatal effects of a choice which he had himself patronised. This exposition of Scripture, said he, will be more hurtful than useful to the people. It is not a new method, replied Zuinglius, it is the ancient method. Recollect the homilies of St. Chrysostom on St. Matthew, and of St. Augustine on St. John. Besides, I will use moderation, and give none any reason to complain.
- 44. Thus Zuinglius abandoned the exclusive use of fragments of the gospel as practised since the days of Charlemagne; re-establishing the Scripture in its ancient rights, he, from the commencement of his ministry, united the Reformation to the primitive ages of Christianity, and prepared a more profound study of the Word of God for ages to come. But he did more. The strong and independent position which he took up in the face of the Church showed that the work in which he had engaged was new. The figure of the Reformer stood out in bold relief to the public eye, and the Reformation advanced. Hoffman, having failed in the chapter, addressed a written request to the provost to prohibit Zuinglius from shaking the popular belief. The provost sent for the new preacher, and spoke to him with great kindness. But no human power could close his lips. On the 31st December, he wrote to the council of Glaris, that he entirely resigned the cure of souls which had hitherto been reserved for him, and gave himself wholly to Zurich, and to the work which God was preparing for him in this town. On Saturday, being new-year's-day, and also the birthday of Zuinglius, who had completed his thirty-fifth year, he mounted the pulpit of the cathedral. A great crowd, eager to see a man who had already acquired so much celebrity, and to hear this new gospel, of which every one began to speak, filled the church. It is to Christ, said Zuinglius, that I wish to conduct you; to Christ, the true source of salvation. His divine word is the only nourishment which I would give to your heart and life. Then he announced that to-morrow, the first Sunday of the year, he would begin to expound the gospel according to St. Matthew. Accordingly, the preacher, and a still larger audience than the day before, were at their posts. Zuinglius opened the gospel—the gospel which had so long been a sealed book—and read the first page, going over the history of the patriarchs and prophets mentioned in the first chapter of St. Matthew, and expounding it in such a way that all were astonished and delighted, and exclaimed, We never heard anything like this.[705]
- 45. THEIR EFFECTS. He continued thus to expound St. Matthew, according to the original Greek. He showed how the whole Bible found at once its exposition and its application in the very nature of man. Delivering the loftiest truths of the gospel in simple language, his preaching reached all classes, the learned and the wise, as well as the ignorant and simple.[706] He extolled the infinite mercies of God the Father, and implored all his hearers to put their confidence in Jesus Christ alone as the only Saviour.[707] At the same time, he earnestly called them to repentance; forcibly attacked the errors which prevailed among the people; fearlessly rebuked luxury, intemperance, extravagance in dress, the oppression of the poor, idleness, foreign service, and foreign pensions. In the pulpit, says one of his companions, he spared no one, pope, emperor, kings, dukes, princes, lords, not even the confederates. All his energy, and all the joy of his heart were in God: accordingly he exhorted all the inhabitants of Zurich to put their confidence in Him only.[708] Never was man heard to speak with so much authority, says Oswald Myconius, who with joy and high hopes watched the labours of his friend. The gospel could not be preached in vain in Zurich. A continually increasing multitude of men of all classes, and more especially of the common people, flocked to hear him.[709] Several Zurichers had ceased to attend on public worship. I derive no benefit from the discourses of these priests, often exclaimed Füsslin, a poet, historian, and counsellor of state; they do not preach the things of salvation; for they do not comprehend them. I see nothing in them but covetousness and voluptuousness. Henry Räuschlin, treasurer of state, one who diligently read the Scriptures, was of the same opinion: The priests, said he, met in thousands at the Council of Constance ... to burn the best man among them. These distinguished men, led by curiosity, went to hear Zuinglius' first sermon. Their countenances bespoke the emotion with which they followed the orator. Glory to God! said they, on coming out; this is a preacher of the truth. He will be our Moses to deliver us from
- 46. OPPOSITION. Egyptian darkness.[710] From this moment they became the Reformer's intimate friends. Powers of the world, said Füsslin, cease to proscribe the doctrine of Christ! After Christ the Son of God was put to death, sinners were raised up. And now, should you destroy the preachers of truth, you will see their places supplied by glaziers, carpenters, potters, founders, shoemakers, and tailors, who will teach with power.[711] In Zurich, at the outset, there was only one shout of admiration, but when the first moment of enthusiasm was over, the adversary resumed courage. Worthy persons alarmed at the idea of a Reformation, gradually drew off from Zuinglius. The violence of the monks which had been veiled for an instant, reappeared, and the college of canons resounded with complaints. Zuinglius stood immovable. His friends beholding his courage, felt in his presence as if a man of apostolic times had reappeared.[712] Among his enemies, some scoffed and jeered; others uttered insulting menaces, but he endured all with Christian patience.[713] Whoso, he was wont to say, would gain the wicked to Jesus Christ must wink at many things,[714]—an admirable saying which ought not to be lost sight of. His character and general bearing towards all contributed as much as his discourses to win their hearts. He was at once a true Christian and a true republican. The equality of mankind was not with him a mere watchword; it was written on his heart and manifested in his life. He had neither that pharisaical pride, nor that monastic gruffness, which are equally offensive to the simple and the wise of the world. Men were drawn towards him, and felt at ease when conversing with him. Strong and mighty in the pulpit, he was affable to all whom he met in the streets, or in the public squares. At the places where the merchants or incorporations met he was often seen among the citizens expounding the leading points of Christian doctrine, or conversing familiarly with them. He gave the same
- 47. TASTE FOR MUSIC. STUDIOUS HABITS. cordial reception to peasant and patrician. He invited country folks to dine with him, says one of his bitterest enemies, walked with them, spoke to them of God, made the devil enter into their hearts and his writings into their pockets. He even went so far that the leading persons in Zurich visited those peasants, entertained them, and walked over the town with them, showing them all sorts of attention.[715] He continued to cultivate music with moderation, says Bullinger: nevertheless the enemies of the gospel took advantage of it, and called him The evangelical flute and lute player.[716] Faber having one day reproached him with his fondness for music, Zuinglius, with noble candour, replied, My dear Faber, you know not what music is. I have, it is true, learned to play on the lute, the violin, and other instruments, and am able by these means to pacify little children;[717] but you of course are too holy for music. Do you not know that David was a skilful player on the harp, and in this way drove the evil spirit out of Saul? ... Ah! if you knew the sound of the heavenly lute, the evil spirit of ambition and avarice by which you are possessed would come out of you also. Perhaps this was Zuinglius' foible, though it was in a spirit of cheerfulness and Christian liberty that he cultivated this art, which religion has always associated with her sublimest flights. He set some of his Christian poems to music, and did not scruple sometimes to amuse the youngest of his flock with his lute. He showed the same good nature to the poor. He ate and drank, says one of his contemporaries, with all who invited him,—he despised no one; he was most compassionate to the poor; always firm and always joyful in bad as in good fortune. No evil made him afraid; his words were at all times full of energy, and his heart full of consolation.[718] Thus Zuinglius increased in popularity—after the example of his Master, seated alternately at the table of the common people and the banquet of the great, but still constantly intent on the work to which God had called him.
- 48. INDULGENCES. At the same time he was an indefatigable student. In the morning, till ten, he read, wrote, and translated: Hebrew in particular engaged his attention. After dinner he attended to those who had any thing to tell him, or any advice to ask of him: took a walk with his friends and visited his hearers. At two he resumed his studies. He took a short walk after supper, and afterwards wrote letters which often occupied him till midnight. He always stood when he studied, and did not allow himself to be interrupted unless on important business. [719] But the labours of a single individual were not sufficient. A person, named Lucian, one day came to him with the writings of the German Reformer. He had been sent by Rhenan, a learned man, then resident at Bâle, and indefatigable in circulating the Reformer's writings throughout Switzerland. Rhenan had become aware that the hawking of books was an important means of diffusing evangelical doctrine. Lucian had travelled almost over the whole of Switzerland, and knew everybody. See, said Rhenan to Zuinglius, whether this Lucian has the necessary prudence and ability; if he has, let him go from town to town, burgh to burgh, village to village, and even from house to house, among the Swiss, with Luther's writings, especially his exposition on the Lord's Prayer, written for the laity.[720] The more he is known the more purchasers will he find. But care must be taken not to let him hawk other books. If he has none but Luther's, his sale of them will be the greater. Thus the humble roof of many a Swiss family was penetrated with some rays of light. There was one other book, however, which Zuinglius should have caused to be hawked with those of Luther—the Gospel of Jesus Christ.
- 49. SAMSON AT BERNE AND BADEN. CHAP. VII Indulgences—Samson at Berne—Samson at Baden—The Dean of Bremgarten—Young Henry Bullinger—Samson and the Dean—Internal struggles of Zuinglius—Zuinglius against Indulgences—Samson dismissed. Zuinglius had not long to wait for an opportunity of displaying his zeal in a new vocation. Samson, the famous indulgence merchant, was slowly approaching Zurich. This miserable trafficker had come from Schwitz to Zug, 20th September, 1518, and had remained there three days. An immense crowd had gathered round him. The poorest were the most eager, so that they prevented the rich from coming forward. This did not suit the monk; accordingly, one of his attendants began to bawl out to the populace, Good people, do not throng so! Let those come who have money. We will afterwards try to content those who have none. From Zug Samson and his band repaired to Lucerne; from Lucerne to Underwald; then crossing the fertile Alps with their rich valleys, passing beneath the eternal ice of Oberland, and in these spots, the grandest in Switzerland, exposing their Roman merchandise, they arrived near Berne. The monk was at first prohibited to enter the town, but succeeded at last in obtaining an introduction by means of persons whom he had in his pay. Exhibiting his wares in the church of St. Vincent he began to cry louder than ever. Here, said he to the rich, are indulgences on parchment for a crown. There, said he to the poor, are indulgences on ordinary paper for two farthings! One day, a celebrated knight, James de Stein, came up prancing on a dapple grey horse; the monk greatly admired the horse. Give me, says the knight, an indulgence for myself, for my troop of five hundred strong, for all my vassals of Belp, and all my ancestors; I will give
- 50. you my dapple grey horse in exchange. It was a high price for the horse, but the courser pleased the Franciscan, and the bargain was struck. The horse went to the monk's stable, and all these souls were declared for ever exempted from hell.[721] Another day, he give a burgher, for thirteen florins, an indulgence, in virtue of which his confessor was authorised to absolve him from any species of perjury. [722] So much was Samson in repute, that Counsellor May, an enlightened old man, having said something against him, was obliged to go down on his knees, and ask pardon of the arrogant monk. This was the monk's last day, and a loud ringing of bells announced his immediate departure from Berne. Samson was in the church standing on the steps of the high altar. Canon Henry Lupulus, formerly Zuinglius's master, was acting as his interpreter. When the wolf and the fox rendezvous together in the field, said canon Anselm, turning to the Schulthess of Walleville, the best thing for you, worthy Sir, is to put your sheep and geese in safety. But the monk cared little for these sarcasms, which, besides, did not reach his ear. Kneel, said he to the superstitious crowd, repeat three Paters, three Ave Marias, and your souls will forthwith be as pure as at the moment of baptism. Then all the people fell upon their knees. Samson wishing even to outdo himself, exclaimed, I deliver from the torments of purgatory and hell all the spirits of the departed Bernese, whatever may have been the manner and place of their death. These jugglers, like those at fairs, kept their finest feat for the last. Samson set out with a heavy purse towards Zurich, crossing Argovia and Baden. The farther on he got, the monk, whose appearance on passing the Alps was so shabby, proceeded with more pride and splendour. The Bishop of Constance, irritated that Samson had not employed him to legalise his bulls, had forbidden all the curates of his diocese to open their churches to him. At Baden, nevertheless, the curate durst not long oppose his traffic. This redoubled the monk's effrontery. Making the round of the burying ground at the
- 51. THE DEAN OF BREMGARTEN. HENRY BULLINGER. head of a procession, he seemed to fix his eyes on some object in the air, while his acolytes sung the hymn for the dead, and pretending to see souls flying from the burying ground to heaven, he exclaimed—Ecce volant! See how they fly. One day, an inhabitant of the place getting up into the church steeple, a great number of feathers were soon seen in the air falling down on the astonished procession; See how they fly, exclaimed the wag of Baden, shaking a feather cushion from the steeple. Many began to laugh.[723] Samson fell into a rage, and could not be appeased till he learned that the individual was subject to fits of derangement: he left Baden in a huff. Continuing his journey, he arrived, towards the end of February, 1519, at Bremgarten, at the solicitation of the Schulthess and second curate, who had seen him at Baden. No individual in that district had a higher reputation than dean Bullinger of Bremgarten. Though far from enlightened as to the errors of the Church and the Word of God, being open, zealous, eloquent, kind to the poor, and ready to do a service to the humblest, he was loved by every body. He had in his youth formed a connection with the daughter of a counsellor of the place. This was the usual expedient of such of the priests as were unwilling to live in general licentiousness. Anna had borne him five sons, but this had in no way lessened the respect which the dean enjoyed. There was not in Switzerland a more hospitable house than his. A great lover of the chace, he was seen surrounded with ten or twelve dogs, and accompanied by the barons of Hallwyll, the abbot Mury, and the gentry of Zurich, scouring the fields and forests around. He kept open table, and none of his guests was more jovial than himself. When the deputies to the Diet were on their way to Baden, on passing through Bremgarten they failed not to take their seats at the dean's table. Bullinger, said they, keeps court like the most powerful baron.
- 52. SAMSON AND THE DEAN. In this house strangers remarked a child of an intelligent countenance. Henry, one of the dean's sons, from his earliest years, had many narrow escapes. Having been seized with the plague, preparations were making for his funeral when he showed some signs of life, and was restored to his delighted parents. On another occasion, a wandering beggar, having won him by caresses, was carrying him off from his family, when some persons in passing recognised and rescued him. At three years of age he could repeat the Lord's prayer and the apostles' creed. One day having slipt into the church, he got into his father's pulpit, stood up gravely, and at the full stretch of his voice, cried out, I believe in God the Father, and so on. At twelve, he was sent to the Latin school of Emmeric, his heart overwhelmed with fear; for those times were dangerous for a young boy without experience. When the students of an university thought its discipline too severe, they not unfrequently left it in troops, carrying the children with them, and encamped in the woods, from which they sent the youngest of their number to beg, or sometimes with arms in their hands they rushed forth on the passing traveller, robbed him, and then consumed their booty in debauchery. Henry was happily kept from evil in this distant abode. Like Luther, he gained his livelihood by singing before the houses, for his father wished to teach him to live by his own shifts. He was sixteen when he opened a New Testament. I found in it, says he, every thing necessary for man's salvation, and thenceforth I laid it down as a principle to follow the Holy Scriptures alone, and reject all human additions. I believe neither the fathers nor myself, but explain Scripture by Scripture, without adding any thing or taking any thing away.[724] God was thus preparing this young man who was one day to succeed Zuinglius. He is the author of the manuscript journal which we often quote. About this time Samson arrived at Bremgarten with all his train. The bold dean undismayed by this petty Italian army, prohibited the monk from vending his wares in his neighbourhood. The Schulthess, town clerk, and second pastor, Samson's friends, had met in a room
- 53. INTERNAL WRESTLINGS OF ZUINGLIUS. of the inn at which he had alighted, and were standing quite disconcerted around the impatient monk. The dean arrived—Here are the papal bulls, said the monk to him, open your church. The Dean.—I will not allow the purses of my parishioners to be emptied by means of letters not authenticated, for the bishop has not legalised them. The Monk (in a solemn tone).—The pope is above the bishop. I enjoin you not to deprive your flock of this distinguished grace. The Dean.—Should it cost me my life, I won't open my church. The Monk (with indignation).—Rebellious priest! in the name of our most holy lord the pope, I pronounce against you the greater excommunication, and will not absolve you till you ransom your unheard-of audacity at the price of three hundred ducats.... The Dean (turning on his heel and retiring).—I will know how to answer before my lawful judges: as for you and your excommunication I have nothing to do with them. The Monk (transported with rage).—Impudent brute! I am on my way to Zurich, and will there lay my complaint before the deputies of the Confederation.[725] The Dean.—I can appear there as well as you, and this instant I set out. While these things were taking place at Bremgarten, Zuinglius, who saw the enemy gradually approaching, kept preaching vigorously against indulgences.[726] Vicar Faber of Constance encouraged him, promising him the bishop's support.[727] I know, said Samson, while proceeding towards Zurich, that Zuinglius will attack me, but I will stop his mouth. Zuinglius was in truth too
- 54. much alive to the value of pardon by Christ not to attack the paper indulgences of these men. Often, like Luther, he trembled because of sin; but in the Saviour found deliverance from his fears. This modest but brave man was advancing in the knowledge of God. When Satan frightens me, said he, by crying to me: You do not this, and you do not that, and yet God commands them!—immediately the soft voice of the gospel consoles me, saying: What thou canst not do (and assuredly thou canst do nothing,) Christ does for thee. Yes, continues the pious evangelist, when my heart is agonised because of my powerlessness, and the feebleness of my flesh, my spirit revives at the sound of this glad news: Christ is thy innocence! Christ is thy righteousness! Christ is thy salvation! Thou art nothing, thou canst do nothing! Christ is the Alpha and the Omega! Christ is all, and can do all.[728] All created things will forsake and deceive thee, but Christ, the Holy and Righteous One, will receive and justify thee.... Yes, exclaims Zuinglius, He is our righteousness, and the righteousness of all who shall ever appear as righteous before the judgment seat of God!... Indulgences could not stand a moment when confronted with such truths; and hence Zuinglius never hesitated to attack them. No man, said he, is able to forgive sins. Christ alone, very God and very man, is able to do it.[729] Go, buy indulgences ... but rest assured you are not at all forgiven. Those who vend forgiveness of sins for money are the companions of Simon Magus, the friends of Balaam and the ambassadors of Satan. Dean Bullinger, still warm from his conference with the monk, arrived at Zurich before him. He came to complain to the Diet against this shameless dealer and his traffic. Envoys from the bishop had arrived for the same purpose. They made common cause, and promised to support each other. The spirit which animated Zuinglius breathed upon this town, and the council of State resolved to oppose the monk's entry into Zurich.
- 55. SAMSON DISMISSED. Samson had arrived in the suburbs, and alighted at an inn. One foot was already on the stirrup preparatory to his entry, when deputies from the council arrived, and while making the customary offer of wine to him as a papal envoy, intimated to him that he might dispense with appearing in Zurich. I have something to communicate to the Diet in the name of his holiness, replied the monk. It was a trick. However, it was resolved to admit him; but as he spoke only of his bulls he was dismissed, after being compelled to retract the excommunication which he had pronounced against the dean of Bremgarton. He went off in a rage, and the pope shortly after recalled him to Italy. A car drawn by three horses, and loaded with the money of which his lies had robbed the poor, preceded him on the steep tracts of St. Gothard, which eight months before he had crossed in poverty, without style, merely the bearer of a few papers. [730] On this occasion the Helvetic showed more firmness than the Germanic Diet. The reason was, because no cardinals and bishops sat in it. Hence the pope deprived of these supports dealt more gently with Switzerland than Germany. In other respects, the affair of indulgences, which played so important a part in the Reformation of Germany, is only an episode in that of Switzerland.
- 56. GOD'S TIME CHAP. VIII. The Labours of Zuinglius—The Baths of Pfeffers—God's time— The Great Death—Zuinglius seized with the Plague—His Enemies—His Friends—Convalescence—General Joy—Effect of the Plague—Myconius at Lucerne—Oswald encourages Zuinglius—Zuinglius at Bâle—Capito called to Mentz—Hedio at Bâle—An Unnatural Son—Preparation for Battle. Zuinglius did not spare himself. His many labours called for some relaxation, and he was ordered to the baths of Pfeffers. Ah! said Herus, one of the pupils who lodged with him, and who thus expressed the feeling of all who knew Zuinglius, had I a hundred tongues, a hundred mouths, a brazen throat, as Virgil expresses it; or rather had I the eloquence of Cicero, how could I express all I owe you, and all that I feel at this separation.[731] Zuinglius, however, set out and reached Pfeffers through the astonishing gorge formed by the impetuous torrent of the Jamina. He descended into that infernal abyss, as the hermit David called it, and arrived at the baths, which are perpetually agitated by the dashing of the torrent, and bedewed by the spray of its foaming water. Where Zuinglius lodged it was so dark that candles were burnt at mid-day. He was even assured by the inmates, that frightful phantoms sometimes appeared in the darkness. Even here Zuinglius found opportunity to serve his Master. His affability won the heart of several of the patients, among others a celebrated poet, Philip Ingentinus, professor at Friburg, in Brigau,[732] who thenceforward became a zealous supporter of the Reformation. God watched over his own work, and was pleased to hasten it. Zuinglius' defect lay in his strength. Strong in body, strong in
- 57. ZUINGLIUS ATTACKED BY THE PLAGUE. character, strong in talents, he was to see all these varieties of strength broken, that he might thereby become such an instrument as God loves to employ. He stood in need of a baptism, that of adversity, infirmity, feebleness, and pain. Such a baptism Luther had received at that period of agony when the cell and long passages of the convent of Erfurt resounded with his cries. Zuinglius was to receive it by being brought into contact with sickness and death. The heroes of this world—the Charles Twelfths and Napoleons—have a moment which is decisive of their career and their glory, and it is when they all at once become conscious of their strength. There is an analogous moment in the life of God's heroes, but it is in a contrary direction; it is when they recognise their impotence and nothingness; thenceforth they receive strength from on high. Such a work as that of which Zuinglius was to be the instrument is never accomplished by man's natural strength; it would immediately wither away like a tree transplanted after its full growth, and when in full leaf. A plant must be feeble in order to take root, and a grain of corn must die in the ground before it can yield a full return. God led Zuinglius, and with him the work of which he was the stay, to the gates of the grave. It is from among bones and darkness, and the dust of the dead, that God is pleased to take the instruments, by means of which he illumines, regenerates, and revives the earth. Zuinglius was hidden among the immense rocks which hem in the furious torrent of the Jamina, when he unexpectedly learned that the plague, or as it was termed the great death,[733] was at Zurich. This dreadful scourge broke out in August, on St. Lawrence day, lasted till Candlemas, and carried off two thousand five hundred persons. The young people who lodged with Zuinglius had immediately left, conformably to directions which he had given. His house was empty, but it was to him the very moment to return. He hurriedly quitted Pfeffers, and reappearing in the bosom of his flock, now decimated by the plague, he immediately sent to Wildhaus for his young brother Andrew, who wished to attend him. From that moment he devoted himself entirely to the victims of this dreadful
- 58. scourge. Every day he preached Christ and his consolations to the sick.[734] His friends delighted to see him safe and sound in the midst of so many fatal darts,[735] still felt a secret alarm. Conrad Brunner, who himself died of the plague a few months after, writing him from Bâle said; Do good, but at the same time remember to take care of your life. It was too late: Zuinglius was seized with the plague. The great preacher of Switzerland was stretched on a bed from which, perhaps, he was never again to rise. He communed with himself, and turned his eye heavenward. He knew that Christ had given him a sure inheritance, and disclosing the feelings of his heart in a hymn remarkable for unction and simplicity, of which, not being able to give the antique and expressive phraseology, we have endeavoured to preserve the rhythm and literal meaning, he exclaimed:— My door has opened ... Death appears.[736] My God! my strength! Dispel all fears! Oh, Jesus! raise Thy pierced arm, And break the sword That caused alarm. But if my soul In life's mid-day Thy voice recalls,[737] Then I obey. Ah! let me die, For I am thine; Thy mansions wait Such faith as mine.
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