L-selectin and chemokine response after liver ischemia and reperfusion

Background L-selectin plays an important role in the early phase of PMNs re cruitment in the hepatic microvasculature following liver ischemia and repe rfusion (I/R). Leukocyte cytokine chemoattractants (chemokines) cause polym orphonuclear neutrophil (PMN) activation in I/R injury. In this study, me e xamined the role of L-selectin in the production of chemokines in the Liver and lung inflammatory response following 90 min of warm ischemia, Study design. Thirty-six C57BL/6 mice were subjected to partial liver ische mia for a period of 90 min. Three groups of animals were included (n = 12 p er group)-sham group, ischemic control, and the ischemic group receiving mo noclonal antibody against L-selectin. We evaluated at 3 h: liver injury mea surements, serum chemokines (MIP-2 and MIP-1 alpha), liver and lung tissue myeloperoxidase (MPO), and liver and lung histology. statistical analysis i ncluded ANOVA, Student-Newman-Keuls', and Kruskal-Wallis multiple compariso n Z-value tests. Results. The ischemic group treated with anti-L-selectin showed significant decreases in liver enzyme levels and a marked decrease in serum MIP-2 (P < 0.05) when compared to ischemic controls. No reduction in serum MIP-1 alph a was noted; however, neutrophil infiltration was significantly ameliorated in the liver and in the lung, as reflected by decreased MPO levels (P < 0. 05). Improved histopathological features were observed in the anti-L-select in-treated group compared to ischemic controls in the Liver and the lung. Conclusions. Our study suggests an important role for L-selectin in the pat hogenesis of Liver I/R and the production of chemokines. Anti-L-selectin tr eatment resulted in improved liver function, decreased neutrophil infiltrat ion, and decreased MIP-2 chemokine response. (C) 2000 Academic Press.