This is particularly true regarding possible beneficial roles of certain mast cell products in these disorders. and symptoms of disease within minutes of exposure to the associated allergens. However, such individuals also typically develop long-term changes in the affected tissues, often called tissue remodeling, Azimilide after repeated exposure to these allergens over periods of weeks to years. There is consensus Azimilide that antigen-specific IgE antibodies, together with one of the major effector cells of allergy, the mast cell (Box 1), can be crucial for the development of the acute manifestations of Rabbit polyclonal to Neuropilin 1 these allergic disorders. But there is less agreement about the role of IgE and mast cells in the chronic, long-term tissue changes that account for much of the morbidity of these increasingly prevalent diseases. Azimilide Box 1 The basics of IgE antibodies and mast cells in allergy Antigen-dependent activation of tissue mast cells that have specific IgE bound to their surface is the central event in acute allergic reactions. IgE, the immunoglobulin isotype with by far the lowest concentration in the circulation, is unable to fix complement and has little ability to cross the placenta. Its plasma concentrations can be markedly elevated in some individuals with allergic diseases or parasite infections1. IgE is thought to mediate biological functions primarily by binding to FcRI, CD23 and other receptors that are expressed on mast cells and other hematopoietic cells1,2. The binding of antigen-specific IgE to FcRI sensitizes mast cells and other effector cells to release mediators in response to subsequent encounters with that specific antigen or with crossreactive antigens1C3. Binding of antigen-IgE immune complexes to CD23 or FcRI can serve to amplify IgE-associated immune responses by facilitating antigen presentation through CD23 on B cells or by antigen focusing through FcRI on dendritic cells or other antigen-presenting cells, leading to the production of IgE to additional epitopes of the antigens that are contained in such immune complexes1,2. However, it is thought that the most crucial function of IgE in allergic diseases is its ability to sensitize mast cells to release biologically active mediators in an antigen-specific manner. Mast cells are distributed throughout virtually all vascularized tissues in vertebrates, with relatively high numbers occurring near body surfaces, including the Azimilide airway epithelium63,97 Along with dendritic cells, mast cells are one of the first immune cells to interact with allergens and other environmentally derived substances. Unlike granulocytes, mature mast cells do not ordinarily circulate in the blood; instead, hematopoietic stem cellCderived circulating mast cell precursors migrate to the peripheral tissues, where they complete their differentiation and maturation and take up residence79. Mast cells are potentially Azimilide long-lived cells, and their number, distribution, phenotype and function can be regulated by many factors whose local concentrations can change at the sites of innate or adaptive immune responses78. In response to activation by IgE through FcRI and specific antigens or by many other endogenous or exogenous substances, mast cells can produce diverse mediators that can promote or downregulate inflammation and influence tissue remodeling and function. IgE1C3 and mast cells4C7 have each been the topic of recent reviews. We focus here on aspects of the biology of IgE and mast cells that we think are most relevant to their proven or potential roles in allergic disorders, especially asthma. We discuss evidence indicating that IgE and mast cells, acting either individually or in concert, can have both nonredundant and partially redundant roles in the pathogenesis of chronic and acute manifestations of asthma. We also.