VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site

Cytokine-activated human endothelial cells express vascular cell adhesion molecule-1 (VCAM-1), which binds lymphocytes. We now identify the integrin VLA-4 as a receptor for VCAM-1 because VLA-4 surface expression on K-562 cells (following transfection of the VLA α⁴ subunit cDNA) resulted in specific cell adhesion to VCAM-1, and anti VLM4 antibodies completely inhibited VCAM-1-dependent cell-cell attachment. In addition, VLA-4 expression allowed K562 cells to attach to the heparin 11 binding region (FN-40) of fibronectin. However, VLA-41VCAM-1 and VLA-4/FN-40 interactions are readily distinguishable: only the former was inhibited by the anti VLA-4 monoclonal antibody HP1/3, and only the latter was inhibited by soluble FN40. The VCAM-1/VLA-4 ligand-receptor pair may play a major role in the recruitment of mononuclear leukocytes to inflammatory sites in vivo.