Effects Of CXCL10 On Liver NK Cells In MHV-3-induced Mice Hepatic Failure

OBJECTIVE Many current studies have revealed that NK cell plays an essential role in the pathological process of HBV induced human fulminant hepatic failure(FHF) and acute-on-chronic liver failure(ACLF). The chemokine/chemokine receptor pathway can trigger a migration of natural killer cells towards virus infected liver tissue. This study is to investigate the effect of chemokine receptor CXCR3 and its ligand CXCL10 on NK cells and to explore the concrete mechanism that how NK cells migrate to liver in virus-induced FHF.METHODS A mice FHF model was established through peritoneal infection with 100 PFU MHV-3 into female Balb/cJ mice of 4-6weeks. The chemotactic effects of both CXCL10 and MHV-3 infected hepatocytes on NK cells seperated from spleen, marrow and peripheral blood were measured by Transwell chemotactic test and flow cyometry. The activation of NK cells by CXCL10 was assessed by detecting the CD69 expression.and the IFN-γand TNF-αlevels .RESULTS A notable NK chemotaxis of MHV-3 infected hepatocytes was observed, and the chemotaxis can be partly blocked by anti-CXCL10 mAb. Being stimulated by CXCL10, the CD69 expression and the IFN-γand TNF-αlevels of NK cells did not present a remarkable variation. CONCLUSION In MHV-3 induced FHF, chemokine receptor CXCR3 and chemokine CXCL10 may play a partial but significant role in the process that NK cells migrate to the liver. The CXCL10 protein has no direct activation on NK cells in vitro.