ALCOHOL & ALVEOLAR MACROPHAGE DYSFUNCTION

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Although bacterial pneumonia is one of the leading causes of death amongst alcoholics, little knowledge exists concerning alcohol-related changes in pulmonary defense mechanisms against inhaled pathogens. The overall goal of this proposed research is to evaluate pulmonary defense mechanisms in animals who have ingested alcohol. Mice will be administered alcohol either acutely, via intragastric gavage, or chronically, by placing the alcohol in the diet. Following ingestion, alteration in pulmonary defenses will be analyzed on cellular and tissue levels in the presence or absence of bacterial endotoxin. Special emphasis will be placed on alterations in alveolar macrophage function. Because of their strategic location in the lung, pulmonary alveolar macrophages play a central role in the response of the lung to inhaled pathogens. Following alcohol ingestion and/or pulmonary endotoxin exposure, macrophage function will be evaluated, in vitro, by measuring alterations a) in plasma membrane integrity, b) in phagocytosis, c) in superoxide production and d) in the ability of the macrophages to secrete mediators (cytokines and products of arachidonic acid metabolism) of inflammation. Whole lung response will be evaluated by a) examining bronchoalveolar lavages for the presence of inflammatory cells and mediators, b) morphometrically evaluating the site and extent of lung injury following exposure and c) in vivo microscopic evaluation of inflammatory processes occurring in the pulmonary microvasculature. Data obtained from these experiments should aid in determining the site(s) of alcohol induced dysfunction in pulmonary defense mechanisms.