P-selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver

Hepatic damage following ischemia-reperfusion injury involves polymorphonuc lear leukocytes (PMN) and platelet sequestration, however the mechanisms of adhesion remain elusive. In this study, using gene-targeted deficient mice , we evaluated P-selectin and its contribution to PMN and platelet adhesion in hepatic damage. In an ill vivo warm ischemia model, hepatic injury was assessed by serum transaminase levels, survival, PMN adhesion by histologic al analysis, and platelet sequestration by immunostaining, Serum transamina se levels were strikingly reduced (by up to threefold) in the P-selectin de ficient mice, particularly at 90 minutes of ischemia, when compared with wi ld-type controls. PMN adhesion and platelet sequestration was also signific antly decreased in P-selectin deficient mice following 90 minutes of partia l ischemia, Animal survival was significantly improved after 75 minutes of total hepatic ischemia in P-selectin deficient mice when compared with wild -type mice. Survival was also achieved after 90 minutes of ischemia in the mutant mice whereas none of the wild-type animals survived. These data show that P-selectin plays a critical role in PMN and platelet adhesion followi ng ischemia-reperfusion injury to the liver.