Kurkijärvi R, Adams D H, Leino R, Möttönen T, Jalkanen S, Salmi M
National Public Health Institute, Turku University, Finland.
J Immunol. 1998 Aug 1;161(3):1549-57.
Vascular adhesion protein-1 (VAP-1) is a dimeric 170-kDa endothelial transmembrane molecule that under normal conditions is most strongly expressed on the high endothelial venules of peripheral lymph nodes and on hepatic endothelia. It is a glycoprotein that mediates tissue-selective lymphocyte adhesion in a sialic acid-dependent manner. In this study, we report the detection of a soluble form of VAP-1 in circulation. We developed a quantitative sandwich ELISA using novel anti-VAP-1 mAbs and used it to determine the levels of soluble VAP-1 (sVAP-1) in the serum of healthy individuals and in patients with inflammatory diseases. In healthy persons, circulating sVAP-1 concentrations were 49 to 138 ng/ml. Immunoblotting studies revealed that the apparent molecular mass of dimeric sVAP-1 is slightly (approximately 10 kDa) higher than that of transmembrane VAP-1 under nonreducing conditions. In contrast, the electrophoretic mobilities of monomeric sVAP-1 and transmembrane VAP-1 were similar after reduction and boiling. Adhesion assays showed that the circulating sVAP-1 modulates lymphocyte binding to endothelial cells. Inflammation can cause an elevation of serum sVAP-1 levels, because sVAP-1 concentrations in patients with certain liver diseases were two- to fourfold higher than those in normal individuals. In contrast, rheumatoid arthritis and inflammatory bowel diseases were not associated with elevated levels of sVAP-1. These findings indicate that there is a functionally active, soluble form of VAP-1 in circulation and suggest that the serum level of sVAP-1 might be a useful marker of disease activity in inflammatory liver diseases.
血管黏附蛋白-1（VAP-1）是一种二聚体的170 kDa内皮跨膜分子，在正常情况下，它在外周淋巴结的高内皮微静脉和肝内皮上表达最为强烈。它是一种糖蛋白，以唾液酸依赖的方式介导组织选择性淋巴细胞黏附。在本研究中，我们报告了在循环中检测到可溶性形式的VAP-1。我们使用新型抗VAP-1单克隆抗体开发了一种定量夹心ELISA，并用于测定健康个体和炎症性疾病患者血清中可溶性VAP-1（sVAP-1）的水平。在健康人中，循环sVAP-1浓度为49至138 ng/ml。免疫印迹研究表明，在非还原条件下，二聚体sVAP-1的表观分子量比跨膜VAP-1略高（约10 kDa）。相反，还原和煮沸后，单体sVAP-1和跨膜VAP-1的电泳迁移率相似。黏附试验表明，循环中的sVAP-1可调节淋巴细胞与内皮细胞的结合。炎症可导致血清sVAP-1水平升高，因为某些肝病患者的sVAP-1浓度比正常个体高两到四倍。相比之下，类风湿性关节炎和炎症性肠病与sVAP-1水平升高无关。这些发现表明，循环中存在功能活跃的可溶性VAP-1形式，并提示sVAP-1的血清水平可能是炎症性肝病疾病活动的有用标志物。
