Involvement of CXCR3-associated Chemokines in MHV-3 Induced Fulminant Hepatic Failure  

作　　者：Yong ZOU Ge SONG Lin DING Tao CHEN Hong-wu WANG Wei-ming YAN Xiao-jing WANG Xiao-ping LUO Qin NING 

机构地区：[1]Department of Infectious Disease, Institute of Infectious Disease, Huazhong University of Science and Technology, Wuhan 430030, China [2]Department of Pediatrics, Tongji hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3]Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China

出　　处：《Virologica Sinica》2009年第6期537-544,共8页中国病毒学（英文版）

基　　金：the National Key Basic Research Program of China (2007CB512900, 2005CB522901, 2005CB 522507);the National Science Fund of China (NSFC 30672380, 30571643)

摘　　要：The role of chemokines in murine hepatitis virus strain 3 (MHV-3) induced fulminant hepatic failure (FHF) is not well defined. In this study, we investigated the role of the CXC chemokine receptor 3 (CXCR3)- associated chemokine [monokine induced by IFN-gamma (Mig/CXCL9) and interferon-gamma-inducible protein 10 (IP-10/CXCL10)] in the recruitment of intrahepatic lymphocytes and subsequent fulminant hepatic failure induced by MHV-3. Balb/cJ mice (6-8 weeks, female) were intraperitioneally injected with 100 PFU MHV-3.The proportions and numbers of T cells and NK cells as well as the expression of CXCR3 on T cells and NK cells in the liver, spleen and blood were analyzed by flow cytometry. The hepatic mRNA level of the CXCR3-associated chemokines (CXCL9 and CXCL10) was detected by realtime PCR. A transwell migration assay was used to assess the chemotactic effect of MHV-3-infected hepatocytes on the splenic lymphocytes. Following MHV-3 infection, the number of hepatic NK cells and T cells and the frequencies of hepatic NK cells and T cells expressing CXCR3 increased markedly; however, in the spleen and peripheral blood, they both decreased significantly. Moreover, the hepatic mRNAs levels of CXCL9 and CXCL10 were significantly elevated post infection. The transwell migration assay demonstrated that MHV-3-infected hepatocytes have the capacity to attract and recruit the splenic NK cells and T cells, and CXCL10 plays a key role in lymphocyte mobilization from the spleen. These results suggest that the CXCR3- associated chemokines (CXCL9 and CXCL10) may play animportant role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and hepatic failure in MHV-3 infection.The role of chemokines in murine hepatitis virus strain 3 （MHV-3） induced fulminant hepatic failure （FHF） is not well defined. In this study, we investigated the role of the CXC chemokine receptor 3 （CXCR3）- associated chemokine [monokine induced by IFN-gamma （Mig/CXCL9） and interferon-gamma-inducible protein 10 （IP-10/CXCL10）] in the recruitment of intrahepatic lymphocytes and subsequent fulminant hepatic failure induced by MHV-3. Balb/cJ mice （6-8 weeks, female） were intraperitioneally injected with 100 PFU MHV-3.The proportions and numbers of T cells and NK cells as well as the expression of CXCR3 on T cells and NK cells in the liver, spleen and blood were analyzed by flow cytometry. The hepatic mRNA level of the CXCR3-associated chemokines （CXCL9 and CXCL10） was detected by realtime PCR. A transwell migration assay was used to assess the chemotactic effect of MHV-3-infected hepatocytes on the splenic lymphocytes. Following MHV-3 infection, the number of hepatic NK cells and T cells and the frequencies of hepatic NK cells and T cells expressing CXCR3 increased markedly; however, in the spleen and peripheral blood, they both decreased significantly. Moreover, the hepatic mRNAs levels of CXCL9 and CXCL10 were significantly elevated post infection. The transwell migration assay demonstrated that MHV-3-infected hepatocytes have the capacity to attract and recruit the splenic NK cells and T cells, and CXCL10 plays a key role in lymphocyte mobilization from the spleen. These results suggest that the CXCR3- associated chemokines （CXCL9 and CXCL10） may play an important role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and hepatic failure in MHV-3 infection.

关 键 词：MHV-3 Liver failure CXCR3 CHEMOKINE Flow cytometry 

分 类 号：S858.32[农业科学—临床兽医学] Q51[农业科学—兽医学]