Chemical mediators of inflammation
Download as PPTX, PDF84 likes30,394 views
Chemical mediators of inflammation are endogenous compounds that are released from cells, plasma or damaged tissue and enhance vascular permeability. There are two main types of mediators - cell-derived and plasma-derived. Cell-derived mediators include vasoactive amines, arachidonic acid metabolites, lysosomal components, platelet activating factor, cytokines and free radicals. Plasma-derived mediators are products of the activated kinin, clotting, fibrinolytic and complement systems, such as bradykinin, fibrinopeptides and anaphylotoxins. These mediators cause effects like vasodilation, increased vascular permeability, smooth muscle contraction and chemotaxis.
Chemical mediators of inflammation
- 2. CHEMICAL MEDIATORS OF INFLAMMATION Also called as permeability factors or endogenous mediators of increased vascular permeability Large and increasing number of endogenous compounds which can enhance vascular permeability Chemical mediators are released from cells, plasma, or damaged tissue
- 3. 1. CELL DERIVED MEDIATORS Vasoactive amines (Histamine, 5-hydroxy tryptamine, neuropeptides) Arachidonic acid metabolites (Eicosanoids) Metabolites via cyclo-oxygenase pathway (prostaglandins, thromboxane A2,prostacyclin,resolvins) Metabolites via lipo-oxygenase pathway (5- HETE,leukotrienes,lipoxins) Lysosomal components (from PMNs ,macrophages) Platelet activating factor Cytokines(IL-1,TNF-α,TNF-β,Chemokines ) Free radicals (oxygen metabolites ,nitric oxide)
- 4. 2. PLASMA DERIVED MEDIATORS Products of The kinin system The clotting system The fibinolytic system The complement system
- 5. 1. CELL DERIVED MEDIATORS 1. VASOACTIVE AMINES ¡) Histamine Stored in the granules of mast cells, basophils and platelets. Main actions Vasodialation, incresed vascular permeability, itching, pain ¡¡) 5-Hydroxytryptamine Present in tissues like chromaffin cells of GIT, spleen, nervous tissue, mast cells and platelets.
- 6. ¡¡¡)Neuropeptides Produced in the central and peripheral nervous systems. Main actions ¡) Increased vascular permeability ¡¡) Trasmission of pain stimuli ¡¡¡) Mast cell degranulation
- 7. 2. ARACHIDONIC ACID METABOLITES (EICOSANOIDS) • Arachidonic acid (fatty acid) is released from the cell membrane by phospholipases. • It is then activated to form arachidonic acid metabolites or eicosanoids by one of the following two pathways: cyclo - oxygenase and lipo – oxygenase pathway
- 8. Metabolites via cyclo oxygenase pathway Activated arachidonic acid Cyclo-oxygenase PGG2 PGH2 + Free oxygen radical PGD2,PGE2 Vasodilator Bronchodilator ↑ permeability PGF2-α Vasodilator bronchoconsticto r TXA2 Vasoconstictor Bronchoconstrict or Platelet aggregation PGI2 Vasodilator Bronchodilator Anti- aggregating agent RESOLVINS Inhibitor of pro- inflammatory cytokines
- 9. • Metabolites via lipo oxygenase pathway Activated arachidonic acid Lipo -oxygenase 5-HPETE 5-HETE LTA4 LTB4 Chemotactic Cell adherence LTC4 LTD4 LTE4 LIPOXINS Smooth muscle constrictor Vasoconstrictor Bronchoconstrictor ↑Vascular permeability
- 10. 3. LYSOSOMAL COMPONENTS The inflammatory cells neutrophils and monocytes contain lysosomal granules which on release elaborate a variety of mediators. ¡) Granules of monocytes and tissue macrophages On degranulation these cells release acid proteases, collagenase , elastase and plasminogen activator
- 11. ¡¡)Granules of neutrophils PRIMARY SECONDAR Y TERTIARY Contain myeloperoxidase, acid hydrolases, acid phosphatase, phospholipase, elastase and protease. Contain Alkaline phosphatase, gelatinase, collagenase, lysozyme, vitamin b12, binding proteins Contain Gelatinase and acid hydrolase.
- 12. 4. PLATELET ACTIVATING FACTOR (PAF) Released from IgE sensitised basophils or mast cells, leucocytes, endothelium and platelets. ACTIONS Increased vascular permeability Vasodialation and vasoconstiction Bronchoconstriction Adhesion of leucocytes to endothelium Chemotaxis
- 13. 5. CYTOKINES These are polypeptide substances produced by activated lymphocytes (lymphokines) and activated monocytes (monokines) Major cytokines- interleukin-1(IL-1), tumour necrosis factor (TNF)α and β, Chemokines. ACTIONS IL-1 and TNF-α, TNF-β Induce endothelial effects- • Increased leucocyte adherece • Thrombogenicity • Fibroblastic proliferation
- 14. IFN-Y • Activation of macrophages and neutrophils • Synthesis of nitric acid synthase Chemokines • IL-8 Chemotactic for neutrophils • Eotaxin chemotactic for eosinophil
- 15. 6. FREE RADICALS:OXYGEN METABOLITES AND NITRIC OXIDE. ¡)Oxygen derived metabolites Released from activated neutrophils and macrophages. ACTIONS • Endothelial cell damage and there by increased vascular permeability • Activation of protease and inactivation of antiprotease causing tissue matrix damage
- 16. ¡¡)Nitric oxide (NO) Formed by activated macrophages ACTIONS • Vasodialation • Anti-platelet activating agent
- 17. 2. PLASMA DERIVED MEDIATORS These include the various products derived from activation and interaction of 4 interlinked systems: kinin, clotting, fibinolytic and complement. oHageman factor(factor xii) of clotting system plays a key role in interactions of the 4 systems. oActivation of factor xii in vivo by contact with basement membrane and bacterial endotoxins, and in vitro with glass or kaolin leads to activation of clotting, fibrinolytic, and kinin systems. oThe end products of the activated clotting, fibrinolytic and kinin system activate the
- 18. Factor XII contact Factor XII a FIBRINOLYTIC SYSTEM CLOTTING SYSTEM KININ SYSTEM Plasminogen Prothrombin Plasma prekallikrein prekallikrein Plasminogen activator activator Thrombin Kallikrein Plasmin Fibrin Kininogen Fibrin split products Bradykinin COMPLEMENT SYSTEM Permeability factors (C3a, C5a), MAC (C5b,C9)
- 19. BRADYKININ ACTIONS Smooth muscle contraction Vasodilation Increased vascular permeability Pain FIBRINOPEPTIDES Increased vascular permeability Chemotaxis Anticoagulant activity
- 20. THE COMPLEMENT SYSTEM I. The activation of complement systemcan occur by: i. Classic pathway via non immunological agents ii. Alternate pathway via non immunological agents Complement system on activation yields activated products – anaphylotoxins (C3a, C4a, C5a) and membrane attack complex (MAC) – C5b, C6, C7…. ACTIONS C3a, C5a,C4a activate mast cells and basophils C3b is an opsonin C5a is chemotactic for leucocytes