title: Alcoholic lung injury: metabolic, biochemical and immunological aspects.
abstract: Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse. Both the oxidative pathways, however, are associated with oxidative stress due to the formation of acetaldehyde and/or reactive oxygen species (ROS). Alcohol ingestion is also known to cause endoplasmic reticulum (ER) stress, which can be mediated by oxidative and/or non-oxidative metabolites of ethanol. An acute as well as chronic alcohol ingestions impair protective antioxidants, oxidize reduced glutathione (GSH, cellular antioxidant against ROS and oxidative stress), and suppress innate and adaptive immunity in the lungs. Oxidative stress and suppressed immunity in the lungs of chronic alcohol abusers collectively are considered to be major risk factors for infection and development of pneumonia, and such diseases as ARDS and COPD. Prior human and experimental studies attempted to identify common mechanisms by which alcohol abuse directly causes toxicity to alveolar epithelium and respiratory tract, particularly lungs. In this review, the metabolic basis of lung injury, oxidative and ER stress and immunosuppression in experimental models and alcoholic patients, as well as potential immunomodulatory therapeutic strategies for improving host defenses against alcohol-induced pulmonary infections are discussed.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: Lata
authors.initials: L
authors.lastname: Kaphalia
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
mesh_terms: D056704:Adaptive Immunity; D000437:Alcoholism / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D012128:Respiratory Distress Syndrome / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism; D012307:Risk Factors
keywords: ER stress; Ethanol; Lung; Metabolism; Oxidative stress
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