Alcohol-induced inhibition of alveolar macrophage oxidant release in vivo and in vitro.
Alcohol consumption is known to predispose the host to more frequent and severe bacterial infections, suggesting that alcohol compromises the normal immune function of the lung. The pulmonary alveolar macrophage is the resident host defense cell in the lung and forms the first line of defense against invading microorganisms. One of the mechanisms whereby alveolar macrophages kill bacteria is by releasing toxic oxygen radical species, such as superoxide anion and hydrogen peroxide. We hypothesized that chronic alcohol consumption caused alveolar macrophage dysfunction leading to inhibition of oxidant production when stimulated. Our data demonstrate that alveolar macrophages harvested from alcohol-treated rats release significantly lower quantity (p < 0.05) of both superoxide anion and hydrogen peroxide when stimulated with several different types of stimuli including heat-killed Staphylococcus aureus, soluble immune complexes or phorbol myristate acetate. Pair-fed control rats who received isocaloric quantities of maltose dextrin in their diet to compensate for the alcohol were able to produce oxidants in equal quantities when stimulated, to rats who were fed a normal diet. Similar results were noted in vitro experiments when alveolar macrophages harvested from normal rats were incubated in vitro in alcohol-containing media and then stimulated with the aforementioned stimuli. Alveolar macrophages, which had been incubated in alcohol for 4 hr, showed significant decreases in their ability to produce superoxide anion. This defect was noticeable for a period up to 8 hr following removal of alveolar macrophages from the alcohol-containing media.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Veterans Administration Medical Center, Indianapolis, IN 46202.
V B
VB
Antony
S W
SW
Godbey
J W
JW
Hott
S F
SF
Queener
D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D006861:Hydrogen Peroxide