title: Neutrophil depletion and chemokine response after liver ischemia and reperfusion.
abstract: Neutrophils play a major role in the hepatic microvasculature following liver ischemia and reperfusion (I/R). Leukocyte cytokine chemoattractants (chemokines) are produced by neutrophils and cause neutrophil activation in I/R injury. We examined the role of neutrophils in the production of chemokines in the liver and lung inflammatory response following liver I/R. C57BL/6 mice were subjected to partial liver ischemia for 90 min. Four groups of animals were included: sham group, sham group with neutrophil depletion, ischemic control group, and ischemic control with neutrophil depletion. We evaluated at 3 h liver injury measurements, serum macrophage inflammatory protein-2 (MIP-2) and macrophage inflammatory protein-1 alpha (MIP-1alpha) chemokines, liver and lung tissue myeloperoxidase (MPO), and liver and lung histology. Statistical analysis included analysis of variance (ANOVA), and Student-Newman-Keuls and Kruskal-Wallis multiple comparison Z-value tests. Ischemic controls showed a significant increase in liver enzyme levels along with statistically significant higher liver and lung MPO activity values than the rest of the other groups (p < .05). MIP-2 values were higher in the ischemic control group when compared to the ischemic neutrophil depleted group. MIP-1alpha levels showed opposite results, being significantly lower (p < .05) in the ischemic control as compared to the neutrophil-depleted group. Improved liver and lung histopathological features were observed in the ischemic neutrophil depleted group when compared to the ischemic control group. Our study confirmed the key role of neutrophils in liver I/R injury and appeared to suggest some relationship between neutrophils and the production of certain chemokines, such as MIP-1alpha, which had an inverse relationship in the absence of neutrophils. Further studies will confirm the validity of these preliminary observations.
authors.affiliation: 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: J E
authors.initials: JE
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; D018925:Chemokines / Q000097:blood*; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008102:Liver Circulation; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D009195:Peroxidase / Q000032:analysis; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D019402:Macrophage Inflammatory Proteins; D009195:Peroxidase