Drugs Acting on Mast Cells Functions: A Cell Biological Perspective

Stefano      Bacci; Paolo      Romagnoli

Abstract

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.

Keywords: Allergy, asthma, atopic dermatitis, histochemistry, mastocytosis, receptors, signal transduction, Mast cells, bone marrow, histamine, heparin, nitric oxide, secreted, pleiotropic cytokines, cell-cell interactions, angiogenesis, fibrosis, autocrine loops, anti-allergic, disodium chromoglycate, glucocorticoids, cyclosporine A, monoclonal antibodies, interferons, JAK3 inhibitors, cytoplasmic granules, haematoxylin, eosin, chromotropic, metachromatically, paracrystalline matrix, piecemeal degranulation, neuroendocrine, arachidonic acid, tumor necrosis factor, fibroblast growth factor, prostaglandins, leukotrienes, thromboxanes, NO synthase, polylysine, polyarginine, G-proteins, immunoglobulin, Src-family kinase, non-T-cell activation linker, phospholypase C, mitogen activated protein kinases (MAPKs), activator protein 1, nuclear factor of activated T cells, phospholypase A2, cyyclooxygenase, phosphatidylinositol 3-kinase (PI3K), diacilglycerol, signal transducer and activator of transcription (STAT)3, 5-lipoxygenase (5LO), cyclic adenosine monophosphate, adenylate cyclase, stem-cell factor, IgE-mediated, keratinocytes, bleomycin, scleroderma, Crohn's disease, nedocromil sodium, transforming growth factor (TGF), chromolyn sodium, atopic eczema, neurofibroma, Corticotropin, Corticotropin release hormone, Adrenergic Agonists, Catecholamines, Phoshodiesterases, Nimesulide, lipopolysaccharide (LPS), Immunophilin Ligands, Opioids, Buprenorphine, Cannabinoids, FcRIIb, cKIT, Omalizumab, Atracurim, vecuronium, Cysteinyl leukotrienes (CysLT), Leukotriene, TNFalpha