Early up-regulation of chemokine expression in fulminant hepatic failure

被引:91
作者
Leifeld, L
Dumoulin, FL
Purr, I
Janberg, K
Trautwein, C
Wolff, M
Manns, MP
Sauerbruch, T
Spengler, U
机构
[1] Univ Bonn, Dept Internal Med 1, D-53105 Bonn, Germany
[2] Hannover Med Sch, Dept Gastroenterol & Hepatol, Hannover, Germany
[3] Univ Bonn, Dept Surg, D-5300 Bonn, Germany
关键词
chemokine; fulminant hepatic failure; fulminant hepatitis; acute liver failure; inflammation;
D O I
10.1002/path.1298
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
CC-chemokines recruit and activate macrophages and T lymphocytes, the major components of inflammatory infiltrates in fulminant hepatic failure (FHF). To analyse the role of CC-chemokines in the pathogenesis of FHF, this study examined serum levels and intrahepatic expression of MCP-1, MIP-1alpha, MIP-1beta, and RANTES in the livers and sera of patients with FHF and controls by ELISA, immunohistochemistry, and competitive RT-PCR. Serum levels and intrahepatic expression of all chemokines studied in FHF exceeded the levels in chronic liver diseases and normal controls. Distinct patterns of expression of each chemokine were noted on Kupffer cells, sinusoidal endothelial cells, hepatocytes, lymphocytes, and bile ducts. Intrahepatic chemokine expression correlated closely with the extent of infiltration by macrophages and T lymphocytes (r = 0.65-0.95, p < 0.001). The functional relationship between intrahepatic chemokine release and infiltration was confirmed in chemotaxis assays by inhibiting chemotaxis induced by homogenates of liver tissue obtained from FHF patients with neutralizing MCP-1, MIP-1alpha, MIP-1beta, and RANTES antibodies. The time course of CC-chemokine release was studied in the concanavalin A and the galactosamine/LPS mouse models of FHF. In both models, intrahepatic chemokine up-regulation occurred as an early event prior to hepatic infiltration and liver damage. The data indicate that an abundant intrahepatic release of CC-chemokines is an early and pivotal step in the pathogenesis of FHE Copyright (C) 2003 John Wiley Sons, Ltd.
引用
收藏
页码:335 / 344
页数:10
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