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A Role for Mast Cells in Alcohol-Induced Tissue Damage and Remodeling

Brittany Law, Charity Fix, Blair Barton and Wayne Carver

Introduction: Alcohol continues to be one of the most frequently abused drugs in the world. While low levels of alcohol consumption may have health benefits, chronic abuse of alcohol deleteriously impacts most body systems and contributes to or exacerbates over sixty disease conditions. The mechanisms of organ and tissue damage in response to alcohol abuse include altered metabolic pathways, accumulation of reactive oxygen species and depressed immune function. Mast cells are multi-functional cells that have been classically described for their role in hypersensitivity reactions. More recently, roles for these cells have been elucidated in innate immunity and tissue remodeling. Mast cells perform these functions primarily through the secretion of a plethora of mediators that include histamine, heparin, serine proteases, cytokines and others. The specific factors that are produced and secreted at any time by mast cells depend in part on the tissue microenvironment providing the basis for extensive plasticity of these cells. Recent studies are beginning to define the role of mast cells in mediating the deleterious effects of chronic alcohol abuse. For instance, alcohol-induced damage to the gastrointestinal mucosa is at least in part mediated by activation of mast cells. Pharmacological inhibition of mast cell degranulation attenuates the increased permeability of the gastrointestinal epithelium associated with alcohol abuse. Conclusion: Mast cells and their secretory products have been implicated in promoting a number of disease conditions. Recent studies have suggested an important role for these cells in alcohol-induced tissue remodeling. These cells and their specific secretory mediators may provide novel therapeutic targets in prevention or reversal of alcohol-induced tissue damage.