© 2000 American Heart Association, Inc.
Cellular Biology |
Human Vascular Adhesion Protein-1 (VAP-1) Plays a Critical Role in Lymphocyte–Endothelial Cell Adhesion Cascade Under Shear
From the MediCity Research Laboratory, University of Turku, and National Public Health Institute, Department in Turku, Turku, Finland.
Correspondence to Dr Marko Salmi, MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland. E-mail marko.salmi{at}utu.fi
Abstract—Lymphocyte binding to vascular endothelium is a prerequisite for the movement of immune cells from the blood into lymphoid tissues and into sites of inflammation. Human vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein involved in this interaction. It also displays an enzymatic (monoamine oxidase) activity. Here we examined how recombinant human VAP-1 mediates lymphocyte binding using rotatory and flow chamber binding assays. VAP-1 cDNA transfected into an endothelial cell line, which does not bind lymphocytes, renders the cell line capable of binding lymphocytes in a shear-dependent manner. VAP-1 transfectants bound lymphocytes 5 times better than monocytes with a preference for T killer cells, and no specific granulocyte adherence was detectable. The binding is partially inhibited by anti–VAP-1 monoclonal antibodies or by blocking lymphocyte L-selectin and CD18 integrins, but not by inhibition of several other homing-associated molecules. In contrast, CD44 ligation on lymphocytes markedly upregulates their VAP-1–dependent adhesion, suggesting that the VAP-1 counterreceptor can be activated via CD44. The transfectant model also allowed us to perform detailed structure-function analyses of VAP-1. We show that the exposed integrin-binding motif RGD or the enzymatic activity is not indispensable for VAP-1–dependent adhesion. Together, these data show that VAP-1 can reconstitute the lymphocyte-endothelial adhesion cascade under shear and propose a critical role for VAP-1 in lymphocyte emigration from the blood.
Key Words: adhesion • leukocyte-endothelial cell interactions • cell trafficking • recruitment • enzymatic activity
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