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

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.