basic chemical mediator

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  1. 1. CHEMICAL MEDIATORS From plasma or cellsFrom plasma or cells Have triggering stimuliHave triggering stimuli Usually have specific targetsUsually have specific targets Can cause a cascade of reactionCan cause a cascade of reaction Are short livedAre short lived
  2. 2. CLASSIC MEDIATORS &THEIR SOURCES
  3. 3. CLASSIC MEDIATORS Vasoactive amines: Histamine, serotonin Complement products Kinins Clotting factors Arachidonic Acid Metabolites: Eicosanoids Nitric oxide Platelet activating factor (paf) Cytokines/Chemokines Lysosome constituents Free radicals Neuropeptides
  4. 4. HISTAMINE Mast Cells, basophils POWERFUL Vasodilator Vasoactive amine
  5. 5. SEROTONIN (5HT, 5-Hydroxy-Tryptamine) Platelets and Entero Chromaffin Cells Also vasodilatation, but more indirect Evokes N.O. synthetase (a ligase) from argenine
  6. 6. COMPLEMENT SYSTEM >20 components, in circulating plasma Multiple sites of action: Leukocyte chemotaxis and activation, Opsonization, Vasodilation (mast cell stimulation) Membrane Attack Complex (MAC)
  7. 7. Complement System
  8. 8. KININ SYSTEM BRADYKININ is KEY component, 9 aas ALSO from circulating plasma ACTIONS Increased permeability Smooth muscle contraction, NON vascular PainPain
  9. 9. CLOTTING FACTORS From circulating plasma Coagulation, i.e., production of fibrin Fibrinolysis Endothelial activation, Leukocyte recruitment
  10. 10. EICOSANOIDS (ARACHIDONIC ACID DERIVATIVES) Part of cell membranes ProstaglandinsProstaglandins (incl. Thromboxanes) LeukotrienesLeukotrienes LipoxinsLipoxins (new) MULTIPLE ACTIONS AT MANY LEVELS
  11. 11. Prostaglandins Pain Fever Clotting
  12. 12. Leukotrienes Chemotaxis Vasoconstriction Increased Permeability
  13. 13. Lipoxins INHIBIT chemotaxis Vasodilatation Counteract actions of leukotrienes
  14. 14. AA Metabolites
  15. 15. Platelet-Activating Factor (PAF) Phospholipid From MANY cells, like eicosanoids ACTIVATE PLATELETS, powerfully Vasodilation, Increased vascular permeability, Leukocyte adhesion, Chemotaxis, Degranulation, Oxidative burst
  16. 16. CYTOKINES/CHEMOKINES CYTOKINES are PROTEINS produced by : MANY cells, But usually LYMPHOCYTES & MACROPHAGES, Numerous roles in acute and chronic inflammation Major cytokines: TNF, IL-1
  17. 17. Major effects of tumor necrosis factor (TNF) and interleukin 1 (IL-1) in inflammation Also; attractants for PMNs
  18. 18. NITRIC OXIDE Produced from the action of nitric oxide synthetase from arginine Potent vasodilator Vascular smooth muscle relaxation; killing of microbes
  19. 19. LYSOSOMAL CONSTITUENTS PRIMARY Also called AZUROPHILIC, or NON-specific Myeloperoxidase Lysozyme (Bact.) Acid Hydrolases SECONDARY Also called SPECIFIC Lactoferrin Lysozyme Alkaline Phosphatase Collagenase
  20. 20. FREE RADICALS O2 (SUPEROXIDE) H2O2(PEROXIDE) OH- (HYDROXYLRADICAL) Phagocytosis: H2O2 +MPO+ Cl = HOCl (hypochlorous radical)
  21. 21. NEUROPEPTIDES Produced in CNS (neurons) SUBSTANCE P NEUROKININ A As vasoactive amines initiate inflammatory responses; Regulate vessel tone, and modulate vascular permeability