CXCR2 Regulates Hepatic Injury after Bile Duct Ligation by Altering Neutrophil Migration

Abstract

IntroductionCXC chemokines and their receptor, CXCR2, are important components for progression of hepatic inflammation. However, the contribution of CXCR2 for cholestatic liver injury have not been elucidated. Neutrophil recruitment in the liver and their releasing reactive oxygen species during cholestasis contribute to liver injury. In the current study, we sought to determine the role of CXCR2 in hepatic injury after bile duct ligation (BDL).MethodsWild‐type (WT) and CXCR2−/− mice were subjected to BDL to induce cholestatic liver injury. Serum and liver samples were obtained 14 days after BDL. Serum levels of alanine amino transferase (ALT) and liver myeloperoxidase content (MPO) were measured. Liver sections were stained with hematoxylin and eosin for assessing the extent of liver necrosis. Neutrophils in liver tissue was determined by immunonhistochemical staining for Ly‐6G.ResultsAfter BDL, CXCR2−/− mice had significantly lower serum ALT level and less necrotic area than WT mice. There was no difference in MPO level in the whole liver, however, the distribution of recruited neutrophils was different between WT and CXCR2−/− mice. In WT mice, neutrophils selectively accumulated to necrotic areas in liver parenchyma and infiltrated into the peri‐biliary lesions. In contrast, in CXCR2−/− mice, neutrophils were randomly scattered in the liver parenchyma, with less concentration of neutrophils in necrotic areas and peri‐biliary lesions.ConclusionThe data suggest that CXCR2 regulates liver injury after BDL by directing neutrophil migration to specific sites of hepatocyte and biliary cell injury.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.