P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in hepatic venules after ischemia/reperfusion

We have recently reported that hepatic ischemia/reperfusion (I/R) is associ ated with a biphasic increase in the expression of P-selectin in the liver microvasculature, with peak expression levels observed at 20 min and 5 h af ter reperfusion. This I/R-induced upregulation of P-selectin expression is accompanied by leukocyte-endothelial cell adhesion in terminal hepatic venu les (THV). The objective of this study was to determine whether the early e xpression of P-selectin contributes to the initial recruitment of rolling a nd adherent leukocytes in THV after liver I/R. Left hepatic lobe ischemia w as induced for 30 min in anesthetized C57BI/6 and P-selectin knockout (KO) mice. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0, 15, 30, 60, and 120 min after reperfusion using intravital v ideo microscopy. Hepatic I/R elicited significant increases in the number o f rolling, saltating, and adherent leukocytes, with peak values observed at 30 min after reperfusion. All of these responses were absent in P-selectin KO mice and in C57B1/6 mice treated with a blocking antibody to P-selectin . Our findings suggest that P-selectin is the primary determinant of leukoc yte-endothelial cell adhesion observed in hepatic venules in the initial pe riod after I/R. Hence, this adhesion molecule may represent a target for th erapeutic intervention in liver transplantation and other conditions associ ated with hepatic I/R.