Regulation of the inflammatory response in asthma by mast cell products.
In airways, mast cells lie adjacent to nerves, blood vessels and lymphatics, which highlights their pivotal importance in regulating allergic inflammatory processes. In asthma, mast cells are predominantly activated by IgE receptor cross linking. In response to activation, preformed mediators that are stored bound to proteoglycans, for example, TNF-alpha, IL-4, IL-13, histamine, tryptase and chymase, are released. New synthesis of arachidonic acid metabolites (leukotriene C4 (LTC4), leukotriene B4 (LTB4) and prostaglandin D2 (PGD2)) and further cytokines is stimulated. Mediators from degranulating mast cells are critical to the pathology of the asthmatic lung. Mast cell proteases stimulate tissue remodelling, neuropeptide inactivation and enhanced mucus secretion. Histamine stimulates smooth muscle cell contraction, vasodilatation and increased venular permeability and further mucus secretion. Histamine induces IL-16 production by CD8+ cells and airway epithelial cells; IL-16 is an important early chemotactic factor for CD4+ lymphocytes. LTC4, LTB4 and PGD2 affect venular permeability and can regulate the activation of immune cells. The best characterized mast cell cytokine in asthmatic inflammation is TNF-alpha, which induces adhesion molecules on endothelial cells and subsequent transmigration of inflammatory leucocytes. IL-13 is critical to development of allergic asthma, although its mode of action is less clear.
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, South Australia, Australia. prue.hart@flinders.edu.au
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D000818:Animals; D001249:Asthma / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D053818:Chymases; D016207:Cytokines / Q000276:immunology; D006632:Histamine / Q000276:immunology; D006801:Humans; D015289:Leukotrienes / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D011453:Prostaglandins / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D015289:Leukotrienes; D011453:Prostaglandins; D006632:Histamine; D012697:Serine Endopeptidases; D053818:Chymases