Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation
Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation
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DOI：
10.1189/jlb.0303093
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发表时间：
2003-09-01
影响因子：
5.5
通讯作者：
Lloyd, AR
中科院分区：
文献类型：
--
作者：
Harvey, CE;Post, JJ;Lloyd, AR
在慢性丙型肝炎病毒感染过程中，影响淋巴细胞向肝小叶转运的因素目前尚不清楚。干扰素-γ诱导蛋白10(IP-10)是一种募集活化T淋巴细胞的趋化因子，最近通过原位杂交显示在慢性丙型肝炎病毒感染时在肝脏中表达。本研究试图通过免疫组织化学方法确定IP-10在肝脏中的细胞来源，检测其受体CXCR3在血液和肝组织分离的T淋巴细胞上的表达，并探讨IP-10的表达与炎症和纤维化的组织学标志之间的关系。IP-10在肝细胞中表达，但不在肝内其他类型的细胞中表达，并且在小叶炎性区域免疫反应最强。与血液相比，肝脏中的T淋巴细胞表达IP-10受体的比例显著增加。CD8T淋巴细胞几乎均为CXCR3阳性，主要分布于肝小叶。IP-10mRNA的表达与小叶坏死性炎症活动有关，但与汇管内炎症或纤维化无关。这些发现表明，IP-10可能是由丙型肝炎病毒在肝细胞内诱导的，并且可能在慢性丙型肝炎病毒感染的发病机制中起重要作用，因为炎症细胞重新聚集到小叶是疾病进展的重要预测因素。
The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.