Circulating form of human vascular adhesion protein-1 (VAP-1): increased serum levels in inflammatory liver diseases.
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.
Kurkijärvi
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National Public Health Institute, Turku University, Finland. riikka.kurkijarvi@utu.fi
Adams
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Leino
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Möttönen
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Jalkanen
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Salmi
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D000328:Adult; D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood* / Q000737:chemistry / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000737:chemistry / Q000502:physiology; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology; D008107:Liver Diseases / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000276:immunology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D012995:Solubility; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)