Ethanol-induced macrophage apoptosis: the role of TGF-beta

Both clinical and laboratory reports indicate that ethanol addicts are prone to recurrent infections. We hypothesize that ethanol promotes macrophage apoptosis, thus compromising the efficiency of the mononuclear phagocyte system in dealing with infection. We studied the effect of ethanol on macroph...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-03, Vol.162 (5), p.3031-3036
Main Authors: Singhal, P C, Reddy, K, Ding, G, Kapasi, A, Franki, N, Ranjan, R, Nwakoby, I E, Gibbons, N
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Dose-Response Relationship, Drug
Ethanol - pharmacology
Humans
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Macrophages - physiology
Mice
Monocytes - drug effects
Rats
Rats, Sprague-Dawley
Species Specificity
Transforming Growth Factor beta - analysis
Transforming Growth Factor beta - physiology
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Summary:Both clinical and laboratory reports indicate that ethanol addicts are prone to recurrent infections. We hypothesize that ethanol promotes macrophage apoptosis, thus compromising the efficiency of the mononuclear phagocyte system in dealing with infection. We studied the effect of ethanol on macrophage apoptosis. Human monocytes isolated from healthy subjects after an alcohol drinking binge showed enhanced apoptosis (before, 1.2 +/- 0.3% vs after, 28.4 +/- 3.7% apoptotic cells/field). Peritoneal macrophages harvested from ethanol-treated rats also showed increased (p < 0.0001) apoptosis. DNA isolated from peritoneal macrophages of ethanol-treated rats displayed integer multiples of 200 base pairs (ladder pattern). Furthermore, macrophages harvested from ethanol-treated rats had an enhanced expression as well as accumulation of TGF-beta. In in vitro studies, ethanol promoted apoptosis of human monocytes as well as rat peritoneal macrophages. In addition, ethanol enhanced apoptosis of murine macrophages (J774) in a time-dependent manner. The ethanol-induced apoptosis was amplified by LPS and partly attenuated (p < 0.001) by anti-TGF-beta Ab. TGF-beta also promoted macrophage apoptosis in a dose-dependent manner. Moreover, ethanol enhanced TGF-beta protein production by macrophages. These results indicate that ethanol promotes macrophage apoptosis. This effect of ethanol seems to be partly mediated through the generation of TGF-beta by macrophages.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.162.5.3031