A likely effector target of the signaling cascade induced by antecedent ethanol ingestion is P-selectin expression. This adhesive glycoprotein is upregulated in postischemic tissues, where it participates in leukocyte recruitment by supporting leukocyte rolling, a requisite step for both subsequent establishment of stationary adhesive interactions and diapedesis across postcapillary venular endothelium. Ethanol preconditioning prevents P-selectin expression in postischemic tissues by an adenosine- and NO-triggered, oxidant-dependent mechanism. These observations provide the molecular basis for the antiadhesive actions demonstrated by ethanol preconditioning in the setting of I/R.
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Shigematsu, S., Ishida, S., Hara, M., Takahashi, N., Yoshimatsu, H., Sakata, T., and Korthuis, R. J. (2003). Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic. Biol. Med. 34, 810-817.
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Yamaguchi, T., Dayton, C., Shigematsu, T., Carter, P., Yoshikawa, T., Gute, D. C., and Korthuis, R. J. (2002). Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions. Am. J. Physiol. 283, H1019-H1030. The first description of the effect of ethanol to promote the development of an anti-inflammatory phenotype in the microcirculation and the critical role that adenosine A2 receptor—dependent activation of endothelial nitric oxide synthase plays in this adaptive transformation.
Yamaguchi, T., Dayton, C. B., Ross, C. R., Yoshikawa, T., Gute, D. C., and Korthuis, R. J. (2003). Late preconditioning by ethanol is initiated by an oxidant-dependent signaling pathway. Free Radic. Biol. Med. 34, 365-376.
Dr. Korthuis is the Bolm Distinguished Professor and Chairman of the Department of Medical Pharmacology and Physiology at the University of Missouri-Columbia. His research is directed at elucidating the cellular mechanisms that underlie the development of protected phenotypes in the microcirculations of the small intestine and skeletal muscle in response to ischemic preconditioning and antecedent ethanol ingestion. Dr. Korthuis' work is supported by grants from the National Institutes of Health (HL-54797 and DK-43785).
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