Enhanced Pulmonary Expression of CXC Chemokines during Hepatic Ischemia/Reperfusion-Induced Lung Injury in Mice

Background.Hepatic ischemia/reperfusion injury during both hepatic resection and transplantation may lead to local and systemic organ dysfunction. Proinflammatory mediators released by Kupffer cells during the initial phase of ischemia/reperfusion are thought to be involved in the development of neutrophil-mediated lung injury. However, the precise factors involved in lung recruitment of neutrophils are unclear. The objective of current study was to determine whether the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and KC, contribute to pulmonary neutrophil recruitment and injury following hepatic ischemia/reperfusion. Methods.C57BL/6 mice were subjected to 90 min of partial hepatic ischemia and 3, 6, and 9 h of reperfusion. Neutrophil accumulation in lung was assessed by lung content of myeloperoxidase (MPO). MIP-2 and KC mRNA were measured using RT–PCR. Lung edema was quantified by wet to dry weight ratios. Results.Three hours after hepatic reperfusion, serum levels of tumor necrosis factor-α were increased. Lung expression of both MIP-2 and KC mRNA was also increased at this time. Both MIP-2 and KC mRNA expression remained elevated 9 h after reperfusion, although levels of MIP-2 mRNA were significantly lower than at 3 h. Pulmonary recruitment of neutrophils was increased within 3 h after reperfusion, but returned to baseline levels by 9 h. Lung edema was increased 3 and 9 h after reperfusion. Neutralization of MIP-2 or KC with antibody significantly decreased lung edema 9 h after reperfusion. Conclusions.These data suggest that mediators released during hepatic ischemia/reperfusion induce the expression of MIP-2 and KC in the lung. In addition, it appears that MIP-2 and KC contribute to lung neutrophil accumulation and the associated pulmonary injury following hepatic ischemia/reperfusion.