title: L-Selectin and chemokine response after liver ischemia and reperfusion.
abstract: BACKGROUND
  L-selectin plays an important role in the early phase of PMNs recruitment in the hepatic microvasculature following liver ischemia and reperfusion (I/R). Leukocyte cytokine chemoattractants (chemokines) cause polymorphonuclear neutrophil (PMN) activation in I/R injury. In this study, we examined the role of L-selectin in the production of chemokines in the liver and lung inflammatory response following 90 min of warm ischemia.
  
  
  METHODS
  Thirty-six C57BL/6 mice were subjected to partial liver ischemia for a period of 90 min. Three groups of animals were included (n = 12 per group)-sham group, ischemic control, and the ischemic group receiving monoclonal antibody against L-selectin. We evaluated at 3 h: liver injury measurements, serum chemokines (MIP-2 and MIP-1alpha), liver and lung tissue myeloperoxidase (MPO), and liver and lung histology. Statistical analysis included ANOVA, Student-Newman-Keuls', and Kruskal-Wallis multiple comparison 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-1alpha 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-selectin-treated group compared to ischemic controls in the liver and the lung.
  
  
  CONCLUSIONS
  Our study suggests an important role for L-selectin in the pathogenesis of liver I/R and the production of chemokines. Anti-L-selectin treatment resulted in improved liver function, decreased neutrophil infiltration, and decreased MIP-2 chemokine response.
authors.affiliation: Departments of Surgery Research Sciences and Molecular Biology, Borgess Research Institute, Kalamazoo, Michigan 49001, USA.
authors.forename: G
authors.initials: G
authors.lastname: Martinez-Mier
authors.forename: L H
authors.initials: LH
authors.lastname: Toledo-Pereyra
authors.forename: E
authors.initials: E
authors.lastname: McDuffie
authors.forename: R L
authors.initials: RL
authors.lastname: Warner
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D019041:L-Selectin / Q000502:physiology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000096:biosynthesis*; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology*
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019041:L-Selectin; D009195:Peroxidase