Alveolar Macrophage Dysfunction and Chronic Alcohol Use. Time to Think about Zinc

Abstract

As the resident professional phagocyte in the lungs, the alveolar macrophage plays a central role in the maintenance of alveolar homeostasis, lung host defense, and immune regulation. During health, the alveolar macrophage operates both as an antiinflammatory effector cell that silently removes particulate debris and microbial organisms from the air spaces, and as a sentinel that initiates inflammatory responses when host defense systems are overwhelmed. During inflammation the role of the alveolar macrophage further expands to include clearance of apoptotic cells from sites of injury and initiation of antiinflammatory and tissue repair programs. A growing body of evidence suggests that chronic ingestion of alcohol impairs many of these essential functions, including phagocytosis of bacteria and ingestion of apoptotic cells. It is therefore not surprising that chronic alcohol use places individuals at increased risk for pneumonia and development of acute respiratory distress syndrome (ARDS) (1, 2). In this issue of the Journal, Mehta and colleagues (pp. 716–723) add to their previous work on alcohol-related lung disease by systematically characterizing alveolar macrophages isolated from individuals with alcohol use disorder and carefully matched control subjects (3). In doing so, they highlight important mechanisms that underpin alveolar macrophage dysfunction in the alcoholic lung. These include intracellular zinc deficiency, altered redox state, and impaired signaling through the granulocyte–monocyte colony–stimulating factor (GM-CSF) receptor.