Mast cells, mediators, and symptomatic activation

Abstract

<abstract> <p>Mast cells (MC) are central effectors of allergic disease and distinct subsets with varying amounts of tryptase, chymase, and carboxypeptidase A3, and cathepsin G is distributed throughout the body. Their involvement in a diverse range of non-allergic illnesses mediated by a complex range of preformed and newly synthesized mediators is now increasingly recognized. The latter especially include conditions under the umbrella term of mast cell activation syndrome. In allergic disease, much has been written about the mechanisms by which the early and rapidly acting mediators produce both localized and systemic allergic symptoms. The role of chymase is presently underappreciated but there is increased awareness that MCs contain significant amounts of preformed TNF alpha and synthesize and releases a wide range of inflammatory cytokines such as interleukins (IL) 1β, IL6, IL31, and IL33. These can aggravate itching and perpetuate inflammation and likely contribute to the late constitutional symptoms seen in allergic reactions. Importantly, their involvement helps to clarify the role of MCs in stress and non-parasitic infections. Presently, unexplained is the increasing incidence of significant acute allergic reactions within a relatively short time frame. In this context, there is increasing interest in the environmental, menstrual, endocrine, circadian, and psychological factors that influence MC activation as well as the endocrine pathways involving the renin angiotensin system that oppose hypotension. In non-allergic diseases with normal numbers of MCs, reduced thresholds for activation may be produced by various combinations of life and dietary factors. Diagnosing these conditions is difficult but may be helped by urinary analysis of prostaglandin metabolites. The investigation and management of mastocytosis with and without mutations of c-kit is also relevant to allergic disease and the new medications used may also be helpful in idiopathic anaphylaxis. This knowledge may open a new chapter in human diseases and mast cell regulation.</p> </abstract>