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.
Dayton
Catherine
C
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, School of Medicine in Shreveport, Shreveport, Louisiana 71130, USA.
Yamaguchi
Taiji
T
Kamada
Kazuhiro
K
Carter
Patsy
P
Korthuis
Ronald J
RJ
D000428:Alcohol Drinking; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002227:Carbazoles / Q000494:pharmacology; D002448:Cell Adhesion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D036904:Leukocyte Rolling; D007962:Leukocytes; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D019007:P-Selectin / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D000470:Alkaloids; D053119:Benzophenanthridines; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D019007:P-Selectin; D010617:Phenanthridines; C081021:Go 6976; C016299:chelerythrine; D011493:Protein Kinase C; C070515:bisindolylmaleimide I