Glutathione availability modulates alveolar macrophage function in the chronic ethanol-fed rat.
We have previously demonstrated that chronic alcohol exposure decreases glutathione in the alveolar space. Although alcohol use is associated with decreased alveolar macrophage function, the mechanism by which alcohol impairs macrophage phagocytosis is unknown. In the current study, we examined the possibility that ethanol-induced alveolar macrophage dysfunction was secondary to decreased glutathione and subsequent chronic oxidative stress in the alveolar space. After 6 wk of ethanol ingestion, oxidant stress in the alveolar macrophages was evidenced by a 30-mV oxidation of the GSH/GSSG redox potential (P <or= 0.05). For control macrophages, approximately 80% internalized fluorescent Staphylococcus aureus were added in vitro. In contrast, only 20% of the macrophages from the ethanol-fed rats were able to bind and internalize fluorescent S. aureus. This ethanol-induced decreased capacity for phagocytosis was paralleled by increased apoptosis. When added to the ethanol diet, the glutathione precursors procysteine or N-acetyl cysteine normalized glutathione and oxidant stress in the epithelial lining fluid as well as the alveolar macrophages to control values. This attenuation of oxidant stress was associated with normalization of macrophage phagocytosis and viability. These results suggested that decreased glutathione availability in the alcoholic lung contribute to alveolar macrophage dysfunction via oxidative stress, resulting in not only decreased function but decreased viability.
Brown
Lou Ann S
LA
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA. lbrow03@emory.edu
Ping
Xiao-Du
XD
Harris
Frank L
FL
Gauthier
Theresa W
TW
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000502:physiology*; D006706:Homeostasis; D020287:In Situ Nick-End Labeling; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D018613:Microscopy, Confocal; D018384:Oxidative Stress / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione