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Ethanol-induced macrophage apoptosis: the role of TGF-beta
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA.
Abstract:
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.
Insights
Ethanol consumption increases macrophage apoptosis, weakening the immune system
Area of Science:
- Immunology
- Cell Biology
- Toxicology
Background:
- Clinical and laboratory data link ethanol addiction to recurrent infections.
- Ethanol's impact on the mononuclear phagocyte system's efficiency is under investigation.
- Macrophage apoptosis is a potential mechanism for ethanol-induced immune compromise.
Purpose of the Study:
- To investigate the effect of ethanol on macrophage apoptosis.
- To elucidate the role of transforming growth factor-beta (TGF-beta) in ethanol-induced apoptosis.
Main Methods:
- Assessing apoptosis in human monocytes and rat peritoneal macrophages post-ethanol exposure.
- Analyzing DNA fragmentation patterns in macrophages.
- Evaluating TGF-beta expression and its role in ethanol-induced apoptosis in vitro and in vivo.
Main Results:
- Ethanol significantly increased apoptosis in human monocytes and rat peritoneal macrophages.
- Ethanol exposure led to DNA laddering in rat macrophages, indicative of apoptosis.
- Ethanol enhanced TGF-beta expression and production by macrophages, which also promoted apoptosis.
Conclusions:
- Ethanol promotes macrophage apoptosis, potentially impairing immune response to infections.
- The observed effect is partly mediated by ethanol-induced TGF-beta generation.
- Targeting TGF-beta may offer therapeutic strategies for alcohol-related immune dysfunction.