Thomson A W, Satoh S, Nüssler A K, Tamura K, Woo J, Gavaler J, van Thiel D H
Pittsburgh Transplant Institute, University of Pittsburgh Medical Centre, PA 15213.
Clin Exp Immunol. 1994 Jan;95(1):83-90. doi: 10.1111/j.1365-2249.1994.tb06019.x.
A circulating form of the membrane-bound ICAM-1 (CD54), a ligand for lymphocyte function-associated antigen-1 (LFA-1), has recently been identified in normal human serum. In this study, serum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis and chronic active hepatitis (autoimmune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC, sICAM-1 levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controls. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-1, investigation of ICAM-1 gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-1 mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may be an important source of sICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.
淋巴细胞功能相关抗原-1（LFA-1）的配体——膜结合型细胞间黏附分子-1（ICAM-1，即CD54）的一种循环形式最近在正常人血清中被发现。在本研究中，采用夹心酶联免疫吸附测定法（ELISA）测定了正常健康男女个体以及自身免疫性肝病患者血清中可溶性ICAM-1（sICAM-1）的水平。原发性胆汁性肝硬化（PBC）、原发性硬化性胆管炎和慢性活动性肝炎（自身免疫性）患者的sICAM-1水平与正常健康受试者相比显著升高。PBC患者的sICAM-1中位数水平约为正常水平的7倍。然而，在非活动性酒精性肝硬化患者中也检测到sICAM-1显著升高，这表明肝脏清除功能受损可能至少部分解释了自身免疫性肝病患者血清水平升高的现象。在PBC患者中，sICAM-1水平与疾病严重程度的综合评估（Child-Pugh分级）相关，并且与肝功能的血清生化指标显著相关，包括胆汁淤积和肝细胞损伤的指标。相比之下，E-选择素的血清水平与健康对照无显著差异。尽管有人提出外周血单个核细胞（PBMC）可能是sICAM-1的来源，但通过逆转录聚合酶链反应对ICAM-1基因表达的研究显示，正常个体和活动性PBC患者的PBMC中ICAM-1信息的基础水平相似。这表明PBMC可能不是该疾病中sICAM-1的重要来源。在PBC患者和对照的经刀豆蛋白A（Con A）刺激的培养淋巴细胞中发现ICAM-1 mRNA表达有类似增加。值得注意的是，用促炎细胞因子和内毒素刺激培养的正常人肝细胞可诱导ICAM-1在细胞表面表达，并使sICAM-1分泌/脱落到肝细胞培养基中。这一新发现表明，肝细胞可能是自身免疫性和其他慢性肝病中sICAM-1的重要来源。sICAM-1在炎症性疾病中的可能作用仍有待确定。
