HUMAN BLOOD DENDRITIC CELLS - BINDING TO VASCULAR ENDOTHELIUM AND EXPRESSION OF ADHESION MOLECULES

To investigate the binding properties of dendritic cells (DC) to vascu lar endothelium, a comparative analysis was undertaken of DC, monocyte s and lymphocytes isolated from the blood of 25 healthy subjects using monolayers of human umbilical vein endothelial cells as the adherence substrate. More blood DC (mean 24% adherence) were adherent to endoth elial monolayers than monocytes (mean 18%; P < 0.001) and lymphocytes (mean 12%; P < 0.001). When the monolayers were pretreated with tumour necrosis factor-alpha (TNF-alpha) all leucocyte populations exhibited an increased attachment, but there was still greater binding of DC (m ean 37% adherence) in comparison with monocytes (mean 23%; P < 0.001) and lymphocytes (mean 18%; P < 0.001). Flow cytometric analysis reveal ed that in relation to monocytes and lymphocytes the DC had a higher s urface expression of the adhesion molecules CD11a (P < 0.05), CD11c (P < 0.005) and CD54 (P < 0.005) but a lower prevalence of cells bearing CD49d (mean 38%; P < 0.05) and the homing receptor CD62L (mean 14%; P < 0.001). CD1a was present on 22% of DC and virtually absent from the surface of monocytes and lymphocytes. The intensity of expression of the beta(1)-integrins, CD49c, CD49d and CD49e was greater on DC than l ymphocytes and monocytes (P < 0.05). Antibody blocking studies demonst rated that DC binding to untreated and TNF-alpha-treated endothelium w as dependent upon the expression of CD11a, CD18 and CD49d, and the sim ultaneous application of anti-CD18 and anti-CD49d antibodies produced an approximate 70% inhibition of adhesion (P < 0.001). Thus, the expre ssion of both beta(1)- and beta(2)-integrins contributes to the adhesi ve interaction between DC and endothelium.