Scientific Research and Essays

  • Abbreviation: Sci. Res. Essays
  • Language: English
  • ISSN: 1992-2248
  • DOI: 10.5897/SRE
  • Start Year: 2006
  • Published Articles: 2740

Full Length Research Paper

Chemokine receptor 3 (CXCR3) and its ligands contribution to virus-induced acute hepatic failure

Yong Zou
  • Yong Zou
  • Department of Blood Transfusion, The 3rd Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China.
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Junjie Bao
  • Junjie Bao
  • Department of Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou 510180, China.
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Yuesi Zhong
  • Yuesi Zhong
  • Department of Hepatobiliary Surgery, The 3rd Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China.
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  •  Accepted: 31 May 2013
  •  Published: 04 September 2013

Abstract

The role of chemokines in virus-induced acute hepatic failure is not well defined. In this study, we investigated the role of CXC chemokine receptor 3 (CXCR3) and its ligands chemokine Mig/CXCL9 (monokine induced by IFN-gamma) and IP-10/CXCL10 (interferon-gamma-inducible protein 10) in the recruitment of intrahepatic lymphocytes and subsequent acute hepatic failure. Balb/cJ mice (6 to 8 weeks, female) were intraperitoneally injected with 100 PFU murine hepatitis virus strain 3 (MHV-3). The proportions and numbers of T cells and NK cells in liver, spleen, and blood as well as the expression of CXCR3 on T cells and NK cells post MHV-3 infection was 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 and CXCL10 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 indicate that interactions involving CXCR3 and its ligands (CXCL9 and CXCL10), especially CXCL10 may play a key role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and acute hepatic failure.

 

Key words: Chemokine, interferon gamma-inducible protein 10 (CXCL10), hepatic failure, natural killer cell, T cell.