A survey of the currently known mast cell mediators with potential relevance for therapy of mast cell-induced symptoms

Abstract

Mast cells (MCs) occupy a central role in immunological as well as non-immunological processes as reflected in the variety of the mediators by which MCs influence other cells. Published lists of MC mediators have all shown only subsets—usually quite small—of the full repertoire. The full repertoire of MC mediators released by exocytosis is comprehensively compiled here for the first time. The compilation of the data is essentially based on the largely cytokine-focused database COPE®, supplemented with data on the expression of substances in human MCs published in several articles, plus extensive research in the PubMed database. Three hundred and ninety substances could be identified as mediators of human MCs which can be secreted into the extracellular space by activation of the MC. This number might still be an underestimate of the actual number of MC mediators since, in principle, all substances produced by MCs can become mediators because of the possibility of their release by diffusion into the extracellular space, mast cell extracellular traps, and intercellular exchange via nanotubules. When human MCs release mediators in inappropriate manners, this may lead to symptoms in any or all organs/tissues. Thus, such MC activation disorders may clinically present with a myriad of potential combinations of symptoms ranging from trivial to disabling or even life-threatening. The present compilation can be consulted by physicians when trying to gain clarity about MC mediators which may be involved in patients with MC disease symptoms refractory to most therapies.

Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children

“…In the nose, sensitized mast cells can be triggered by low-level exposures such as diesel exhaust, tobacco smoke, pesticides, or fragrances. When triggered, they release complex cascades containing nearly 400 inflammatory mediators, which affect physiological, immunological, and inflammatory processes [ 70 , 71 , 72 , 73 ].…”

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

“…The granules store a wide range of preformed mediators, including histamine [ 13 ], proteases such as tryptases and chymases [ 13 , 14 ], and also some cytokines; mainly tumor necrosis factor alpha (TNF-α) [ 15 ]. These substances cause various biological effects, such as increasing vascular permeability, smooth muscle contraction and activation of immune cells, which are associated with symptoms of allergic inflammation [ 16 ]. In addition to the immediate release of preformed mediators, MCs also secrete de novo synthesized compounds that are produced after MC stimulation [ 13 ].…”

Chemical Intolerance and Mast Cell Activation: A Suspicious Synchronicity

“…There is considerable literature describing mast cells (MCs) and their function [36][37][38][39][40][41][42]. Briefly, they are sentinel immunity cells that respond to most bodily invasions and insults.…”

“…Once triggered via any of their large arrays of receptors and activation pathways [39], MCs release variable subsets from a repertoire of hundreds of distinct mediators [38], resulting primarily in inflammation, allergic-like phenomena, and altered tissue growth and development [39,40]. MCs respond to a wide variety of antigenic triggers, causing the release of mediators particular to the insult and its anatomic location [41,42,44].…”

“…These chemicals enter via every conceivable route-the olfactory-limbic tract, the airways, the gastrointestinal tract, the urogenital tract, the skin, and even via injection/implantation. All of these pathways, as well as our blood and lymphatics, are lined with MCs, which lie in wait until a xenobiotic appears [38,42]. If the MCs in that specific tissue have previously been insulted, whether acutely by a major exposure (e.g., a pesticide application) or perhaps repeatedly at lower exposure levels (e.g., by VOCs in a sick or moldy building), they spring into action upon re-exposure, releasing cascades containing potentially hundreds of mediators designed to protect against the invaders.…”