Neutrophil depletion and chemokine response after liver ischemia and reperfusion

Neutrophils play a major role in the hepatic microvasculature following liv er ischemia and reperfusion (I/R). Leukocyte cytokine chemoattractants (che mokines) are produced by neutrophils and cause neutrophil activation in I/R injury. We examined the role of neutrophils in the production of chemokine s 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 an imals were included: sham group, sham group with neutrophil depletion, isch emic control group, and ischemic control with neutrophil depletion. We eval uated at 3 h liver injury measurements, serum macrophage inflammatory prote in-2 (MIP-2) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) chem okines, liver and lung tissue myeloperoxidase (MPO), and liver and lung his tology. Statistical analysis included analysis of variance (ANOVA), and Stu dent-Newman-Keuls and Kruskal-Wallis multiple comparison Z-value tests. Isc hemic controls showed a significant increase in liver enzyme levels along w ith statistically significant higher liver and lung MPO activity values tha n the rest of the other groups (p < .05). MIP-2 values were higher in the i schemic control group when compared to the ischemic neutrophil depleted gro up. MIP-1<alpha> levels showed opposite results, being significantly lower (p < .05) in the ischemic control as compared to the neutrophil-depleted gr oup. Improved liver and lung histopathological features were observed in th e 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 produ ction of certain chemokines, such as MIP-1<alpha>, which had an inverse rel ationship in the absence of neutrophils. Further studies will confirm the v alidity of these preliminary observations.