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*
National Public Health Institute and MediCity Research Laboratory, Turku University, Turku, Finland;
Liver Research Laboratories, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom; and
Department of Internal Medicine, Turku University Central Hospital, Turku, Finland
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
(
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.
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