Circulating Form of Human Vascular Adhesion Protein-1 (VAP-1): Increased Serum Levels in Inflammatory Liver Diseases

• Published in: The Journal of immunology (1950) 1998-08, Vol.161 (3), p.1549-1557
• Main Authors: Kurkijarvi, Riikka, Adams, David H, Leino, Rauli, Mottonen, Timo, Jalkanen, Sirpa, Salmi, Marko
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amine Oxidase (Copper-Containing) - blood; Amine Oxidase (Copper-Containing) - chemistry; Amine Oxidase (Copper-Containing) - physiology; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - immunology; Cell Adhesion - drug effects; Cell Adhesion Molecules - blood; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - physiology; Cholangitis, Sclerosing - blood; Cholangitis, Sclerosing - immunology; Enzyme-Linked Immunosorbent Assay - methods; Female; Humans; Liver Cirrhosis, Biliary - blood; Liver Cirrhosis, Biliary - immunology; Liver Diseases - blood; Liver Diseases - immunology; Liver Diseases - pathology; Liver Diseases, Alcoholic - blood; Liver Diseases, Alcoholic - immunology; Liver Neoplasms - blood; Liver Neoplasms - immunology; Liver Neoplasms - secondary; Male; Middle Aged; Solubility; Up-Regulation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.3.1549

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.