Biological implications of preformed mast cell mediators

Abstract

Mast cells store an impressive array of preformed compounds (mediators) in their secretory granules. When mast cells degranulate, these are released and have a profound impact on any condition in which mast cell degranulation occurs. The preformed mast cell mediators include well-known substances such as histamine, proteoglycans, proteases, and preformed cytokines, as well as several recently identified compounds. Mast cells have recently been implicated in a large number of novel pathological settings in addition to their well-established contribution to allergic reactions, and there is consequently a large current interest in the molecular mechanisms by which mast cells act in the context of a given condition. In many cases, preformed mast cell mediators have been shown to account for functions ascribed to mast cells, and these compounds are hence emerging as major players in numerous pathologies. In this review we summarize the current knowledge of preformed mast cell mediators.

Proteolytic Histone Modification by Mast Cell Tryptase, a Serglycin Proteoglycan-dependent Secretory Granule Protease

“…histamine, serotonin), preformed cytokines (e.g. TNF), and anionic proteoglycans of serglycin type and various MC-specific proteases, the latter including tryptases, chymases, and carboxypeptidase A3 (2)(3)(4). Previous studies have shown that serglycin proteoglycan has a key regulatory role in maintaining the homeostasis of the secretory granules by forming complexes with the various granule proteases and bioactive amines, thereby promoting their storage within granules (5,6).…”

Mast cell chymase modulates IL-33 levels and controls allergic sensitization in dust-mite induced airway inflammation

“…When MCs are activated they may degranulate and thereby release a number of preformed compounds from their secretory granules, including bioactive amines, cytokines, proteoglycans and various MC-specific proteases, the latter encompassing chymases, tryptases and carboxypeptidase A3 2,3 . Activated MCs may also respond by de novo synthesis of additional pro-inflammatory compounds 4 .…”

Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis

“…MCs operate through a wide variety of bioactive mediators that they release in response to activation by, for example, Fc ɛ RI crosslinking (Lundequist and Pejler , 2011 ). Proteases are stored in exceedingly high amounts in the secretory granules of MCs, and they are released as fully active enzymes upon degranulation (Pejler et al , 2007 ).…”