Mast cells are ubiquitous, but are most numerous at anatomic sites that are in contact with the environment, such as in the mucosa of airways and gut, as well as in the skin. Although mast cells have long been identified as key cellular mediators of the allergic inflammatory response, 8-12 they have other physiological functions, including a role in innate immunity. 13-16 Mast cells mediate ‘early-phase’ (e.g. anaphylaxis, acute asthma) and ‘latephase ’ allergic responses, as well as non-type I hypersensi tivity reactions through release of mediators (vide infra). 17 Furthermore, mast cells mediate upregulation of Th2-responses and allergen-specific IgE biosynthesis, which contribute to host defenses against parasitic infections.18,19 Mast cells undergo activation, classically following cross-linking of Fc ε RI-bound IgE by multivalent allergen in sensitized individuals. Non-IgEtriggersformastcellmediator release include anaphylatoxins of the complement system (C3a and C5a), neuropeptides (e.g. vasoactive intestinal peptide, somatostatin, substance P), lipopolysaccharides (LPS), chemokines (e.g. CCL3/MIP1 α), and Tolllike receptors(TLR).13,14,16 Upon activation by either IgE-dependent or -independent mechanisms, the following mediators are released: (1) vasoactive amines, particularly histamine; (2) several distinct tryptases (α, β, and δ) that comprise the principal protein component of mast cells; (3) anionic proteoglycans (e.g. heparin, chondroitin sulphate) that confer metachromasia upon staining with toluidine blue; (4) various lipid mediators, these arachidonic acid-derived eicosanoids, which include leukotriene C4, leukotriene B4, and prostaglandin D2, mediate vasodilation, vasopermeability, smooth muscle constriction, mucus secretion, as well as other proinflammatory processes;(5)otherproteases (e.g. chymase, carboxypeptidaseA);and(6) specific cytokines.9,20-30 The latter recruit and activate specific cells, including basophils (IL-3), eosinophils (IL-5), neutrophils (tumor necrosis factor (TNF)- α /IL-8), and lymphocytes (IL-4/IL-13).
|Original language||English (US)|
|Title of host publication||Chronic Myeloproliferative Disorders|
|Number of pages||13|
|State||Published - Jan 1 2008|
ASJC Scopus subject areas