Mechanism by which IL-16 generated by mast cells mediates allergic inflammation.

Abstract

Mast cells are the most important effector cells in the modulation of allergic and sterile inflammation (1). The activation of mast cells with specific IgE antibody and antigens or other active compounds such as anaphylotoxin substance P (SP) and cortocotropin releasing hormone (CRH) results in numerous biological effects (1-4). These include the initiation of transcription, translation and secretion of many different cytokines (Table), including interleukin-16 (IL-16), proteases (chymases, tryptase), histamine, leukotrienes and prostaglandin D2 (PGD2) (2). Among the chemotactic factors (5-8), IL-16 which was previously known as lymphocyte chemotattractant factor is potentially involved in the selective recruitment of lymphocytes in the sites of allergic inflammation (9). Mast cell activation induces T-cell migration either directly by the release of chemotactic factors, such as IL16 (10), or indirectly by induction of adhesion molecule expression on endothelial cells. Moreover, T-cells are the major non-epithelial cellular sourse of IL-16 in normal and asthmatic airways (11-14). Eosinophils are also a potential cellular source of IL-16 in asthmatic lungs. Mast cells can generates IL-16 providing a link between mast cell activation and the accumulation of T-cells in mast celldependent inflammation, perpetuating the pathologic process (13). Moreover, IL-16 is one of the earliest CD4+ cell chemoattractants after antigen challenge (14), and have arole in the initiation of cellular, as well as humoral immunity (12). IL-16 a pro-inflammatory cytokine, a ligand for CD4+, is a chemoattractant molecule expressed by lymphocytes (CD8+ and CD4+), eosinophils, mast cells, and lung epithelium (12), macrophages, airway epithelial cells of asthmatics (16). IL-16 is a potent chemoattractant for CD4+ T cells, eosinophils and monocytes mainly derived from activated T cells (17-18). CD4+ T cell infiltration is known to occur in tissues at sites of mast cell activation (19). In addition to being a major effector cell in the elicitation of allergic inflammation, mast cells have been found to be activated in various T cell mediated inflammatory processes and to reside in close physical proximity to T cell. Mast cell activation has been reported to induce T cell migration either directly by the release of chemotactic factors, such as lymphotactin or IL16, or indirectly by the induction of adhesion molecules expression on endothelial cells. Mast cells are able to present antigens to Tcells, resulting in their activation in either MHC class I or class II restricted and co-stimulatory molecule dependent fashion also, T cell derived mediators, such as beta-chemokines directly induce mast cell degranulation (10). IL-16 may play a role in the trafficking of dendritic cells and may be a major chemotactic signal from dendritic cells towards themselves and towards T cells (20). IL-16 functions as a chemoattractant factor for CD4+ cells, as a modulator ofT cell activation,