Cytokine-activated human endothelial cells express vascular cell adhesion molecule-l(VCAM-l), which binds lymphocytes. We now identify the in&grin VLA-4 as a receptor for VCAM-1 because VLA4 surface expfession on K-562 cells (following transfection of the VLA a4 subunit cDNA) resulted in specific cell adhesion to VCAM-1, and antiYLA4 antibodies completely inhibited VCAM-l-dependent cell-cell attachment. In addition, VLA-4 expression allowed K-562 cells to attach to the heparin II binding region (FN-40) of fibronectin. However, VLA-4NCAM-1 and VLR4/FN-40 interactions are readily distinguishable: only the former was inhibited by the antiYLA4 monoclonal antibody HPl13, and only the latter was inhibited by soluble FN-40. The VCAM-lNL&4 iigand-receptor pair may play a major role in the recruitment of mononuclear leukocytes to inflammatory sites in vivo. introduction

Vascular endothelial cells constitute the lining of blood vessels and normally exhibit a low affinity for circulating leukocytes (Harlan, 1965). The release of cytokines at sites of inflammation, and in response to immune reactions, causes their activation and results in the increased expression of a host of surface antigens (Collins et al., 1986; Pober et al., 1986; Bevilacqua et al., 1987; Leeuwenberg et al., 1989). These include the adhesion proteins ELAM-1, which binds neutrophils (Bevilacqua et al., 1987, 1989), and ICAM-1, which interacts with all leukocytes (Dustin et al., 1986; Pober et al., 1986; Boyd et al., 1988; Dustin and Springer, 1988). In addition, we have recently described a new adhesion protein, VCAM-1, which binds lymphocytes (Osborn et al., 1989). These cytokine-induced adhesion molecules appear to play an important role in leukocyte recruitment to extravascular tissues. The integrins are a group of cell-extracellular matrix and cell-cell adhesion receptors exhibiting an ap heterodimeric structure, with a widespread cell distribution and a high degree of conservation throughout evolution (Hynes, 1987; Marcantonio and Hynes, 1988). The integrins have been subdivided into three major subgroups: the p2 subfamily of integrins (LFA-1, Mac-l, and p150, 95) is mostly in-