title: Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a.
abstract: Allergic diseases such as asthma result from inappropriate immunologic responses to common environmental allergens in genetically susceptible individuals. Following allergen exposure, interaction of dendritic cells (DC) with CD4(+) T cells leads to the production of Th2 cytokines, which induce B cells to synthesize IgE molecules (sensitization phase). These IgE molecules bind to their high affinity receptors (FcvarepsilonRI) on the surface of mast cells and basophils and their subsequent cross-linking by allergen results in the release of preformed and newly synthesized mediators, which cause bronchoconstriction, lung inflammation and airway hyperresponsiveness (AHR) in asthma (effector phase). The complement components C3a and C5a levels are increased in the lungs of patients with asthma and are likely generated via the actions of both allergen and mast cell proteases. In vivo studies with rodents have shown that while C3a facilitates allergen sensitization in some models C5a inhibits this response. Despite this difference, both anaphylatoxins promote lung inflammation and AHR in vivo indicating that cells other than DC and T cells likely mediate the functional effects of C3a and C5a in asthma. This review focuses on the contribution of C3a and C5a in the pathogenesis of asthma with a particular emphasis on mast cells and basophils. It discusses the mechanisms by which anaphylatoxins activate mast cells and basophils and the associated signaling pathways via which their receptors are regulated by priming and desensitization.
authors.affiliation: Department of Pathology, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, PA 19104-6030, USA. alih@upenn.edu
authors.forename: Hydar
authors.initials: H
authors.lastname: Ali
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D015550:Cell Degranulation; D015926:Complement C3a / Q000276:immunology / Q000378:metabolism*; D015936:Complement C5a / Q000276:immunology / Q000378:metabolism*; D003888:Desensitization, Immunologic; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D043562:Receptors, G-Protein-Coupled; D015926:Complement C3a; D015936:Complement C5a