Role of P-selectin expression in hepatic ischemia and reperfusion injury

Background. Researchers have shown that reperfusion of ischemic tissues ini tiates a complex series of reactions that paradoxically injure tissues. Alt hough several mechanisms have been proposed to explain the pathobiology of ischemic/reperfusion (I/R) injury, much attention has focused on adhesion m olecules. Our research is intended to show the kinetics of P-selectin in th e liver in response to I/R injury. Methods. Left-lobar hepatic ischemia was induced for 30 min in 35 C57BL-6 m ice and 30 P-selectin-deficient (K-O) mice. P-selectin expression was measu red in these mice at 20 min, 2, 5, 12 and 24 h reperfusion times, as well a s in control and sham animals. The animals were injected with radio-labeled P-selectin monoclonal antibody and the organs were harvested for counts/g tissue, expressed as the percentage injected dose. Serum liver enzymes were measured and pathological sections of ischemic and control livers were per formed. The unpaired t-test was used for statistical analysis. Results. P-selectin expression showed two peaks in this animal model. The f irst peak was at 20 min and the second peak at 5 h of reperfusion (p < 0.00 1). We documented an 8-fold increase in aspartate aminotransferase (AST), a lanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels 10 h f ollowing I/R injury. Pathological specimens showed periportal necrosis cons istent with an ischemic event. P-selectin I(K-O mice showed no up-regulatio n as a separate control group, and the liver enzymes were significantly low er than the wild-type mice at 10 h (p < 0.001). Conclusion. P-selectin has a bimodal expression following hepatic I/R injur y. The first peak is attributed to the Weibel-Palade bodies and the second to new translational P-selectin. We noted no difference in the up-regulatio n of P-selectin in the ischemic and non-ischemic liver lobes in the same an imal.