Antecedent ethanol ingestion prevents postischemic P-selectin expression in murine small intestine.
OBJECTIVE
Ethanol ingestion 24 h prior to ischemia and reperfusion (I/R) prevents postischemic leukocyte rolling and adhesion in postcapillary venules of the small bowel. Since I/R-induced leukocyte rolling is critically dependent on the expression of P-selectin by endothelial cells lining postcapillary venules, the authors hypothesized that antecedent ethanol consumption would attenuate postischemic expression of this adhesive ligand.


METHODS
To address this postulate, P-selectin expression was evaluated using a dual radiolabeled monoclonal antibody technique in the jejunum of mice that received either distilled water vehicle or ethanol by gavage (dose) on day 1 and then were subjected to sham I/R (nonischemic controls) or I/R (20 min ischemia/60 min reperfusion) 24 h later.


RESULTS
I/R was associated with a 2-fold increase in P-selectin expression relative to nonischemic controls, an effect that was largely abolished by antecedent ethanol ingestion. Exposing the bowel to adenosine deaminase or adenosine A2 receptor antagonists (DMPX or ZM241385), an NO synthase inhibitor (L-NIO) or an NO scavenger (PTIO), or an antioxidant (mercaptoproprionyl glycine) during the period of ethanol exposure on day 1 prevented the beneficial effect of ethanol to limit I/R-induced P-selectin expression, on day 2.


CONCLUSIONS
The data indicate that antecedent ethanol exposure prevents postischemic P-selectin expression on day 2 by a mechanism that is triggered by adenosine A2 receptor activation and the formation of nitric oxide (NO) and reactive oxygen species (ROS) during the period of ethanol exposure on day 1.
Dayton
Catherine
C
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, School of Medicine in Shreveport, Shreveport, Louisiana, USA.
Yamaguchi
Taiji
T
Kamada
Kazuhiro
K
Carter
Patsy
P
Korthuis
Ronald J
RJ
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D019007:P-Selectin / Q000187:drug effects* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D015427:Reperfusion Injury
D019007:P-Selectin; D017382:Reactive Oxygen Species; D043683:Receptors, Adenosine A2; D009569:Nitric Oxide; D000431:Ethanol