Mast cells and nitric oxide: control of production, mechanisms of response

Mast cells are involved in numerous activities ranging from control of the vasculature, to tissue injury and repair, allergic inflammation and host de fences. They synthesize and secrete a variety of mediators, activating and modulating the functions of nearby cells and initiating complex physiologic al changes. Interestingly, NO produced by mast cells and/or other cells in the microenvironment appears to regulate these diverse roles. This review o utlines some of the pathways central to the production of NO by mast cells and identifies many of the tightly controlled regulatory mechanisms involve d. Several cofactors and regulatory elements are involved in NO production, and these act at transcriptional and post-translational sites. Their invol vement in NO production will be outlined and the possibility that these pat hways are critically important in mast cell functions will be discussed. Th e effects of NO on mast cell functions such as adhesion, activation and med iator secretion will be examined with a focus on molecular mechanisms by wh ich NO modifies intracellular signalling pathways dependent or independent of cGMP and soluble guanylate cyclase. The possibility that NO regulates ma st cell function through effects on selected ion channels will be discussed . Metabolic products of NO including peroxynitrite and other reactive speci es may be the critical elements that affect the actions of NO on mast cell functions. Further understanding of the actions of NO on mast cell activiti es may uncover novel strategies to modulate inflammatory conditions. (C) 20 01 Elsevier Science B.V. All rights reserved.