Sano K, Nagaki M, Sugiyama A, Hatakeyama H, Ohnishi H, Muto Y, Moriwaki H
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Dig Dis Sci. 1999 Apr;44(4):796-805. doi: 10.1023/a:1026682329876.
Adhesions of leukocytes to hepatocytes and sinusoidal endothelial cells mediates the induction and progression of hepatic injury. However, in contrast to endothelial cells, information regarding the regulation of interactions between leukocytes and hepatocytes is limited. In the present study, we investigated the effect of inflammatory mediators including lipopolysaccharide (LPS), staphylococcal enterotoxin B (SEB), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) on the adhesion of polymorphonuclear leukocytes or lymphocytes to primary cultured rat hepatocytes, and on the expression of intercellular adhesion molecule-1 (ICAM-1) gene in hepatocytes. Both polymorphonuclear leukocyte and lymphocyte adhesion to hepatocytes were enhanced after exposure of hepatocytes to IFN-gamma and TNF-alpha, but not after exposure to LPS, SEB or IL-1beta. The adhesion induced by either IFN-gamma or TNF-alpha was inhibited by monoclonal antibodies against ICAM-1 or lymphocyte function-associated antigen-1 (LFA-1). Nonstimulated hepatocytes expressed faintly ICAM-1 mRNA, which increased slightly during the culture period. ICAM-1 mRNA expression was up-regulated to a greater extent by incubating hepatocytes with IFN-gamma or TNF-alpha, and peaked after 12 hr of incubation with TNF-alpha and after 24 hr with IFN-gamma. These results indicate that IFN-gamma and TNF-alpha induce the expression of ICAM-1 on parenchymal hepatocytes and that the LFA-1-ICAM-1 pathway plays an important role in the interaction between hepatocytes and neutrophils or lymphocytes.
白细胞与肝细胞及肝窦内皮细胞的黏附介导了肝损伤的诱导和进展。然而，与内皮细胞不同，关于白细胞与肝细胞之间相互作用调节的信息有限。在本研究中，我们研究了包括脂多糖（LPS）、葡萄球菌肠毒素B（SEB）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）在内的炎症介质对原代培养大鼠肝细胞中多形核白细胞或淋巴细胞黏附的影响，以及对肝细胞中细胞间黏附分子-1（ICAM-1）基因表达的影响。肝细胞暴露于IFN-γ和TNF-α后，多形核白细胞和淋巴细胞与肝细胞的黏附均增强，但暴露于LPS、SEB或IL-1β后则无此现象。IFN-γ或TNF-α诱导的黏附被抗ICAM-1或淋巴细胞功能相关抗原-1（LFA-1）的单克隆抗体所抑制。未受刺激的肝细胞微弱表达ICAM-1 mRNA，在培养期间略有增加。用IFN-γ或TNF-α孵育肝细胞可使ICAM-1 mRNA表达上调幅度更大，用TNF-α孵育12小时后及用IFN-γ孵育24小时后达到峰值。这些结果表明，IFN-γ和TNF-α诱导实质肝细胞上ICAM-1的表达，且LFA-1-ICAM-1途径在肝细胞与中性粒细胞或淋巴细胞之间的相互作用中起重要作用。
