Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells.
The regulated interactions of leukocytes with vascular endothelial cells are crucial in controlling leukocyte traffic between blood and tissues. Vascular adhesion protein-1 (VAP-1) is a novel, human endothelial cell molecule that mediates tissue-selective lymphocyte binding. Two species (90 and 170 kD) of VAP-1 exist in lymphoid tissues. Glycosidase digestions revealed that the mature 170-kD form of VAP-1 expressed on the lumenal surfaces of vessels is a heavily sialylated glycoprotein. The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding. We also show that L-selectin is not required for binding of activated lymphocytes to VAP-1 under conditions of shear stress. The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species. These data indicate that L-selectin negative lymphocytes can bind to tonsillar venules via the VAP- 1-mediated pathway. Moreover, our findings extend the role of carbohydrate-mediated binding in lymphocyte-endothelial cell interactions beyond the known selectins. In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions.
Salmi
M
M
National Public Health Institute and MediCity Research Laboratory, University of Turku, Finland.
Jalkanen
S
S
D000328:Adult; D006631:Amine Oxidase (Copper-Containing); D001808:Blood Vessels / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology*; D008970:Molecular Weight; D019158:N-Acetylneuraminic Acid; D009924:Organ Culture Techniques; D014066:Palatine Tonsil / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D011485:Protein Binding; D012794:Sialic Acids / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008024:Ligands; D012794:Sialic Acids; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D019158:N-Acetylneuraminic Acid