VLA-4 INTEGRIN MEDIATES LYMPHOCYTE MIGRATION ON THE INDUCIBLE ENDOTHELIAL-CELL LIGAND VCAM-1 AND THE EXTRACELLULAR-MATRIX LIGAND FIBRONECTIN

We herein tested the ability of lymphocytes to utilize the beta1 integ rin VLA-4 to mediate cell migration when adhering to its cytokine-indu cible endothelial cell ligand VCAM-1 or its extracellular matrix ligan d fibronectin. We used an in vitro system consisting of purified VCAM- 1/Fc fusion protein or fibronectin immobilized on porous polycarbonate membranes to quantitatively measure the migration efficiency of an Ep stein-Barr virus-transformed B cell line (SLA) and T lymphoblasts deri ved from normal donors. We found that both SLA cells and T lymphoblast s migrated across membranes coated with VCAM-1/Fc or fibronectin in a site density-dependent manner. Above and below an optimal site density of VCAM-1/Fc or fibronectin, the migration efficiency decreased. A 6- 20-fold higher number of lymphocytes migrated across membranes coated with VCAM-1/Fc than with fibronectin. The differential migration effic iency is consistent with a higher number of adherent lymphocytes and a higher avidity of adhesion for VCAM-1/Fc than for fibronectin when th e ligands were immobilized on plastic, and is independent of the activ ation state of the cells. These results demonstrated a stringent regul ation of migratory response by cell adhesion strength and a delicate b alance between stationary and migratory behaviors of a cell on the adh esive substrates. Like the beta2 integrin LFA-1, VLA-4 may be a locomo tive adhesion receptor which is involved in the transendothelial migra tion of lymphocytes and the infiltration of lymphocytes into lymphoid or peripheral tissues by binding to VCAM-1 and fibronectin.