Circulating form of human vascular adhesion protein-1 (VAP-1): increased serum levels in inflammatory liver diseases

Research output: Contribution to journalArticle

Authors

  • R Kurkijärvi
  • D H Adams
  • R Leino
  • T Möttönen
  • S Jalkanen
  • M Salmi

Abstract

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.

Details

Original languageEnglish
Pages (from-to)1549-57
Number of pages9
JournalJournal of Immunology
Volume161
Issue number3
Publication statusPublished - 1 Aug 1998

Keywords

  • Adult, Aged, Amine Oxidase (Copper-Containing), Carcinoma, Hepatocellular, Cell Adhesion, Cell Adhesion Molecules, Cholangitis, Sclerosing, Enzyme-Linked Immunosorbent Assay, Female, Humans, Liver Cirrhosis, Biliary, Liver Diseases, Liver Diseases, Alcoholic, Liver Neoplasms, Male, Middle Aged, Solubility, Up-Regulation