Nitric oxide: a regulator of mast cell activation and mast cell-mediated inflammation.
Nitric oxide (NO) plays diverse roles in physiological and pathological processes. During immune and inflammatory responses, for example in asthma, NO is generated at relatively high and sustained levels by the inducible form of nitric oxide synthase (NOS-2). NOS-2 derived NO regulates the function, growth, death and survival of many immune and inflammatory cell types. In the case of mast cells, NO suppresses antigen-induced degranulation, mediator release, and cytokine expression. The action of NO on mast cells is time dependent, requiring several hours, and noncGMP mediated, most probably involving chemical modification of proteins. NO inhibits a number of mast cell-dependent inflammatory processes in vivo, including histamine mediated vasodilatation, vasopermeation and leucocyte-endothelial cell attachment. In human asthma and animal models of lung inflammation the role of NO is harder to define. However, although there are conflicting data, the balance of evidence favours a predominantly protective role for NO. Mimicking or targeting NO dependent pathways may prove to be a valuable therapeutic approach to mast cell mediated diseases.
Coleman
J W
JW
Department of Pharmacology and Therapeutics, University of Liverpool, UK. coleman@liv.ac.uk
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D006152:Cyclic GMP / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine
D016207:Cytokines; D009569:Nitric Oxide; D006493:Heparin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010450:Endopeptidases; D006152:Cyclic GMP