INCREASED ADHESION OF HUMAN MONOCYTES TO IL-4-STIMULATED HUMAN VENOUSENDOTHELIAL-CELLS VIA CD11 CD18, AND VERY LATE ANTIGEN-4 (VLA-4) VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1)-DEPENDENT MECHANISMS

Expression of adhesion molecules on endothelial cells (EC) can be up-r egulated or induced by cytokines. The aim of the present study was to investigate the effect of IL-4 on both the expression of adhesion mole cules on EC and monocyte adhesion to EC. Flow cytometric analysis show ed that VCAM-1 expression on EC was up-regulated after stimulation wit h IL-4 for 24 h, whereas the expression of E-selectin (formerly called endothelial leucocyte adhesion molecule-1 (ELAM- 1)) was not enhanced , and that of intercellular adhesion molecule-1 (ICAM- 1) only slightl y. The adhesion of monocytes to EC increased to maximum values upon st imulation of EC with IL-4 for 24 h. Coating of monocytes with MoAb aga inst the integrin beta2-subunit (CD18) significantly inhibited their a dhesion to IL-4-stimulated EC; maximal inhibition was found when monoc ytes were coated with anti-CD18 MoAb in combination with MoAb against CD49d (the alpha-chain of VLA-4), whereas no inhibition was found when monocytes were coated only with MoAb against CD49d. Monocyte adhesion was not significantly inhibited when IL-4-stimulated EC were coated w ith MoAbs against ICAM-1 or VCAM- 1 alone or in combination. Adhesion of monocytes was inhibited to a greater extent when in addition to coa ting of monocytes with MoAb against CD18 the EC were coated with MoAb against VCAM-1. From these results we conclude that monocytes bind to IL-4-stimulated EC via interaction of CD11/CD18 molecules on the monoc ytes with an as yet unknown endothelial ligand, and interaction of VLA 4 on monocytes with VCAM-1 on EC.