Ethanol blocks leukocyte recruitment and endothelial cell activation in vivo and in vitro

被引:70
作者
Saeed, RW
Varma, S
Peng, T
Tracey, KJ
Sherry, B
Metz, CN
机构
[1] N Shore Long Isl Jewish Res Inst, Med Biochem Lab, Manhasset, NY 11030 USA
[2] N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, Manhasset, NY 11030 USA
[3] N Shore Long Isl Jewish Res Inst, Lab Chemokine Biol, Manhasset, NY 11030 USA
关键词
D O I
10.4049/jimmunol.173.10.6376
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immune system impairment and increased susceptibility to infection among alcohol abusers is a significant but not well-understood problem. We hypothesized that acute ethanol administration would inhibit leukocyte recruitment and endothelial cell activation during inflammation and infection. Using LPS and carrageenan air pouch models in mice, we found that physiological concentrations of ethanol (1-5 g/kg) significantly blocked leukocyte recruitment (50-90%). Because endothelial cell Activation and immune cell-endothelial cell interactions are critical regulators of leukocyte recruitment, we analyzed the effect of acute ethanol exposure on endothelial cell activation in vivo using the localized Shwartzman reaction model. In this model, ethanol markedly suppressed leukocyte accumulation and endothelial cell adhesion molecule expression in a dose-dependent manner. Finally, we examined the direct effects of ethanol on endothelial cell activation and leukocyte-endothelial cell interactions in vitro. Ethanol, at concentrations within the range found in human blood after acute exposure and below the levels that induce cytotoxicity (0.10.5 %), did not induce endothelial cell activation, but significantly inhibited TNF-mediated- endothelial cell activation, as measured b y adhesion molecule (E-selectin, ICAM-1, VCAM-1) expression and chemokine (IL-8, MCP-1, RANTES) production and leukocyte adhesion in vitro. Studies exploring the potential mechanism by which ethanol suppresses endothelial cell activation revealed that ethanol blocked NF-kappaB nuclear entry in an IkappaBalpha-dependent manner. These findings support the hypothesis that acute ethanol overexposure may increase the risk of infection and inhibit the host inflammatory response, in part, by blocking endothelial cell activation and subsequent immune cell-endothelial cell interactions required for efficient immune cell recruitment.
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页码:6376 / 6383
页数:8
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