Alcohol and the Alveolar Macrophage

Abstract

Compared to nonalcoholics, patients with a history of alcohol-use disorders have increased susceptibility to lung infections, leading to sepsis and in a disproportionately high percentage of cases the development of the acute respiratory distress syndrome. A primary cause for increased risk of respiratory infections in alcoholics is impaired immune function of the alveolar macrophage. Macrophages are key components of innate immunity in various tissues and serve as a first line of defense against invading pathogens by generating pro-inflammatory responses to kill microbes and facilitate the clearance of foreign debris from tissues. Macrophages can be characterized into three phenotypes based on their mechanism of activation and functional characteristics: classical activation (pro-inflammatory), alternative activation, and deactivation (the latter two are anti-inflammatory). Alcohol induces an alternatively activated phenotype in alveolar macrophages, which is characterized by increased oxidative stress, via up-regulation of transforming growth factor beta and NADPH oxidases and phagocytic dysfunction. A range of treatments that increase glutathione and zinc bioavailability, granulocyte-macrophage colony-stimulating factor signaling, t)r activation of nuclear factor erythroid 2-related factor 2 for the attenuation of alcohol-induced oxidative stress have been identified as strategies that can restore alveolar macrophage immune function in the alcoholic lung. (PsycINFO Database Record (c) 2016 APA, all rights reserved)