ALCOHOL &ALVEOLAR MACROPHAGE DYSFUNCTION

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.