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 alpha 4 subunit cDNA) resulted in specific cell adhesion to VCAM-1, and
anti-VLA-4 antibodies completely inhibited VCAM-1-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-4/VCAM-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 FN-40. The VCAM-1/VLA-4
ligand-receptor pair may play a major role in the recruitment of mononuclear leukocytes
to inflammatory sites in vivo.