title: Mast cells as targets of pimecrolimus.
abstract: Mast cells, the multi-functional secretory cells, are the pivotal effector cells in immune response, and contribute to the pathogenesis of many diverse diseases, like asthma and mastocytosis, by releasing numerous proinflammatory mediators. Pimecrolimus (SDZ ASM 981) is a derivative of the macrolactam ascomycin and is a member of the calcineurin inhibitor class of immunosuppressors. It inhibits the calcineurin-dependent activation of nuclear factor of activated T cells and the expression of a number of proinflammatory cytokines in turn. Pimecrolimus has high and selective anti-inflammatory activity within the skin, and with much lower potential to affect local and systemic immune responses. Therefore it has been widely used for treatment of various inflammatory skin diseases. It has a cellselective mode of action, and mast cells are its specific target cells. Pimecrolimus inhibits the release of both preformed and de novo synthesized mediators from activated mast cells and inhibits accumulation of mast cells by inducing apoptosis. Several experimental and clinical reports have demonstrated the successful application of pimecrolimus and other calcineurin inhibitors, such as tacrolimus and cyclosporine A, to treat mastocytosis, a spectrum of disorders characterized by mast cell hyperplasia, especially cutaneous mastocytosis. These new findings suggest that pimecrolimus and other calcineurin inhibitors may be a novel and effective therapeutic approach for mast cell-associated diseases such as asthma and mastocytosis.
authors: Division of Allergy/Immunology, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. zcma@labiomed.org
authors: Zhongcai
authors: Z
authors: Ma
authors: Zongjiu
authors: Z
authors: Jiao
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019703:Calcineurin / Q000276:immunology; D065095:Calcineurin Inhibitors; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008415:Mastocytosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015394:Molecular Structure; D016559:Tacrolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065095:Calcineurin Inhibitors; C117268:pimecrolimus; D019703:Calcineurin; D016559:Tacrolimus