title: The role of two distinct endothelial molecules, vascular adhesion protein-1 and peripheral lymph node addressin, in the binding of lymphocyte subsets to human lymph nodes.
abstract: Lymphocyte binding to high endothelial venules (HEV) in noninflamed peripheral lymph nodes (PLN) relies heavily on two endothelial adhesion molecules called vascular adhesion protein-1 (VAP-1) defined by mAb 1B2 and the peripheral lymph node addressins (PNAd) defined by mAb MECA-79. Data from several different groups indicate that these two molecules share several characteristics in expression, biochemical structure, and function, raising the possibility that VAP-1 may be identical to the 170- and 90-kDa species of PNAd glycoproteins. In this study, we show that many PLN HEV coexpress these two molecules. In parallel SDS-PAGE analyses, the m.w. of the 90- and 170-kDa forms of these molecules are indistinguishable. Nevertheless, we show by different metabolic labelings, by reciprocal cross-precipitations, and by immunofluorescence stainings of newly established VAP-1 transfectants that the 90- and 170-kDa species of PNAd and VAP-1 are distinct molecules. In functional terms, VAP-1 is strikingly selective in mediating PLN HEV adhesion of CD8-positive, but not of CD4-positive T cells. In contrast, PNAd contributes to the adhesion of both CD4-positive and CD8-positive cells to these vessels. Together, these data show that initial adhesion of CD8-positive lymphocytes to PLN HEV requires a PNAd- and a VAP-1-dependent step that are both essential and may occur simultaneously or sequentially.
authors.affiliation: MediCity Research Laboratory, University of Turku, Finland. marko.salmi@utu.fi
authors.forename: M
authors.initials: M
authors.lastname: Salmi
authors.forename: J
authors.initials: J
authors.lastname: Hellman
authors.forename: S
authors.initials: S
authors.lastname: Jalkanen
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000954:Antigens, Surface / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000502:physiology*; D008565:Membrane Proteins; D008970:Molecular Weight; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology*; D014162:Transfection / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)