Drugs acting on mast cells functions: a cell biological perspective.

Mast cells are bone marrow derived cells capable of secreting many active molecules: mediators stored in specific granules, such as histamine and heparin; small molecules produced immediately upon stimulation, such as lipid derivatives and nitric oxide; and many constitutively secreted, pleiotropic cytokines. Thanks to these secretion products and perhaps direct cell-cell interactions, mast cells play roles in inflammation and tissue repair, angiogenesis and fibrosis. Mast cells themselves respond to many mediators of their own, giving rise to autocrine loops. Successful anti-allergic therapies have typically targeted the receptors for mast cell secretory products, particularly those for histamine. Among agents directly affecting mast cells, disodium chromoglycate and glucocorticoids are known since some time, while new pharmacological approaches may stem from the recognition of an interference with mast cell growth and differentiation by cyclosporine A, monoclonal antibodies, interferons, and JAK3 inhibitors. The action of agents that affect mast cell differentiation and function is considered here from a cell and tissue biological perspective as a premise to the application of these agents to the clinics, therefore special attention has been paid to references pertaining to humans.