Chemical Notes

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CHEMICAL MEDIATORS OF INFLAMMATION
Cell derived mediators
Mediator| Source| Function|
Vasoactive amines|
Histamine| Mast cells, basophil, platelet| Vasodilation, ↑ vascular permeability, endothelial activation| Serotonin| platelets| Vasodilation, ↑ vascular permeability| Eicosanoids|
Prostaglandins| Mast cells, leukocytes| Vasodilation (PGD2,PGE1,E2 & PGF2-α), pain (PGE2), fever| Thromboxane A2| | Promotes platelet aggregation, vasoconstriction| Prostacyclin| | Inhibits platelet aggregation, vasodilation| Leukotrienes| Mast cells, leukocytes| Vasoconstriction & Increased vascular permeability (C4,D4,E4), chemotaxis (B4), leukocyte adhesion and activation (B4)| Cytokines|

TNF| Macrophages, T cells| (1) Induce fever; induce WBC release from bone marrow.(2) ↑ thrombogenicity (coagulation) of endothelium, aggregation & activation of neutrophil (3) induce liver to synthesise acute phase protein (4) causes apoptosis of cells (5) catabolism of muscle & fat (cachexia)| IL-1| Macrophages, endothelial cells| (1) Chemotaxis, fever, WBC release from marrow, histamine release (2) Induce liver synthesise acute phase protein (3) Activate endothelium, adhesion molecule & permeability (coagulation & inflammation) (3) activate phagocyte, PMN & lymphocyte| IL-6| Macrophage, endothelial, T cell| (1) Induce fever & liver to synthesise acute phase protein (2) stimulate proliferation of B cells (3) activate phagocyte & lymphocyte| IL-8| | (1) histamine release (2) activate endothelium (3) chemotaxis| IL-12| Macrophage, Dentritic cell| (1) ↑ cytotoxic activity & IFN-production of NK cells + T killer cells. (2) Causes TH1 differentiation, Increase TH1 but not TH2 response| IFN-γ| NK cells, T cells| (1) Activate macrophage & stimulate antibody response (2) Activate endothelial cells (3) inhibit haemopoiesis| CSF| | induce WBC release from bone marrow|

Others|
PAF| Macrophage, endothelial cell, mast cell, platelet, PMNs| Platelet aggregation, vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst| ROS| Leukocytes| Killing of microbes, tissue damage|

NO| Endothelium, macrophages| (1) regulates neurotransmitter release & blood flow (2) macrophages use it as a cytotoxic metabolite for killing microbes and tumor cells (3) cause vasodilation & endothelial smooth muscle relaxation (4) Tissue Destruction| Chemokine| T cell, endothelial cell, activated macrophage, fibroblast, platelet, dentritic cell| Chemotaxis, leukocyte activation & integrin affinity| a. Vasoactive amines – Histamine (by mast cell) & Serotonin (by platelet) preformed and released quickly b. Arachidonic acid (PUFA) – located on lipid membrane & is formed via cyclooxygenase & lipoxygenase pathways. Precursor to eicosanoid like prostaglandins, Leukotrienes, and Lipoxins c. Cytokines – polypeptide products of many cell types that mediate: (1) Inflammation (2) Immune responses (3) functions of cells of Mononuclear Phagocyte System (MPS) (4) antibody release & cytotoxicity (5) Local endothelial activation (expression of adhesion molecule), systemic acute-phase response; in severe infections, septic shock Major cytokine in acute inflammation → TNF and IL-1, chemokines. Major cytokine in chronic inflammation → interferon-γ (IFN-γ) & IL-12

Tumor Necrosis Factor and Interleukin-1
Their secretion is stimulated by products of microbes & T cells. Functions: (1) endothelial activation (2) stimulate expression of adhesion molecules on endothelial cells, resulting in increased leukocyte binding and recruitment (3) enhance production of additional cytokines (notably chemokines) & eicosanoids. Interferons

Type 1 IFN → IFN-IFN-
-Produced in response to viral infection
-They inhibit viral replication & cell proliferation, increase NK actibity...
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