Antecedent ethanol ingestion prevents postischemic leukocyte adhesion and P-selectin expression by a protein kinase C-dependent mechanism.

The aim of this study was to determine whether protein kinase C (PKC) contributed to the effects of ethanol ingestion to prevent P-selectin expression, leukocyte rolling (LR), and stationary leukocyte adhesion (LA) induced by subjecting the small bowel to ischemia and reperfusion (I/R) 24 hr later. I/R increased P-selectin expression, LR, and LA, effects that were largely abolished by antecedent ethanol consumption. Exposing the bowel to a specific but nonisoform-selective PKC inhibitor (chelerythrine or bisindolylmaleimide I) during the period of ethanol exposure did not alter the anti-inflammatory effects induced by ethanol ingestion 24 hr prior to I/R. Go-6976, a PKC inhibitor that exhibits a high degree of selectivity for the calcium-dependent PKC isoforms, markedly reduced the effectiveness of antecedent ethanol exposure to abrogate these postischemic inflammatory responses. Our data indicate that antecedent ethanol exposure prevents postischemic P-selectin expression, LR, and LA by a mechanism that involves activation of calcium-dependent PKC isotypes.