C3a and LPS mediated gene regulation in human mast cells examined by microarray and PCR : V-98

Abstract

The mast cells are central effector and regulatory cells in IgE mediated allergic reactions and Th2- dominated immune responses. Binding of antigens to receptor bound IgE results in release of inflammatory mediators such as histamine, leukotriene (LT) C4 and Prostaglandin (PG) D2 (1), in addition to a variety of different TH2 cytokines, including IL-4, IL-5, IL-6, IL-10 and IL-13, which has been implemented in the pathogenesis of allergic reactions. Asthmatic airway inflammation has been strongly linked to Th2 lymphocytes and their cytokines, particularly IL-4, IL-5 and IL-13, which regulate airway hyper responsiveness, eosinophil activation, mucus production and IgE secretion. Mucosal mast cells lie adjacent to nerves, blood vessels and lymphatics, which highlights their pivotal importance in regulating allergic inflammatory processes. In allergic asthma, mast cells are predominantly activated by IgE receptor cross linking, and mediators from degranulating mast cells are critical to the pathology of the asthmatic lung. Mast cell proteases stimulate tissue remodeling, neuropeptide inactivation and enhanced mucus secretion, while histamine stimulates smooth muscle cell contraction, vasodilatation and increased venular permeability and further mucus secretion