The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1998/7/17/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 1, July 1, 1998 17-27

Articles

Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule

David J. Smith*,{ddagger}, Marko Salmi*,{ddagger}, Petri Bono*,{ddagger}, Jukka Hellman§, Taina Leu*,{ddagger}, and Sirpa Jalkanen*,{ddagger}

From the * MediCity Research Laboratories, University of Turku, FIN-20520 Turku, Finland; the {ddagger} National Public Health Institute, FIN-20520 Turku, Finland; and the § Centre for Biotechnology, BioCity, FIN-20520 Turku, Finland

Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin–independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170–180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind lymphocytes, and the binding can be partially inhibited with anti–VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate lymphocyte adhesion and to function as an adhesion receptor involved in lymphocyte recirculation. Its primary function in other locations where it is expressed, such as smooth muscle, may depend on its inherent monoamine oxidase activity.

Key Words: vascular adhesion protein 1 • adhesion molecule • monoamine oxidase • sialoglycoprotein • endothelial

Address correspondence to David Smith, BioTie Therapies Ltd., BioCity, Tykistökatu 6, FIN-20520 Turku, Finland. Phone: 358-2-2748922; Fax: 358-2-2748910; E-mail: david.smith{at}biotie.fi

D. Smith was a postdoctoral fellow of the European Molecular Biology Organisation and subsequently in receipt of a European Community Human Capital and Mobility Fellowship during the course of this work.

T. Leu's current address is Department of Medical Microbiology, University of Turku, FIN-20520 Turku, Finland.

Abbreviations used: BSAO, bovine serum amine oxidase; CHO, Chinese hamster ovary; DAO, diamine oxidase; GCG, Genetics Computer Group; HEV, high endothelial venule(s); MAO, monoamine oxidase; PLN, peripheral lymph node(s); PNAd, PLN addressin; SSAO, semicarbazide-sensitive amine oxidase; VAP-1, vascular adhesion protein 1.


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