VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin.

Abstract

We herein tested the ability of lymphocytes to utilize the beta 1 integrin VLA-4 to mediate cell migration when adhering to its cytokine-inducible endothelial cell ligand VCAM-1 or its extracellular matrix ligand 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 Epstein-Barr virus-transformed B cell line (SLA) and T lymphoblasts derived from normal donors. We found that both SLA cells and T lymphoblasts 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 efficiency is consistent with a higher number of adherent lymphocytes and a higher avidity of adhesion for VCAM-1/Fc than for fibronectin when the ligands were immobilized on plastic, and is independent of the activation state of the cells. These results demonstrated a stringent regulation of migratory response by cell adhesion strength and a delicate balance between stationary and migratory behaviors of a cell on the adhesive substrates. Like the beta 2 integrin LFA-1, VLA-4 may be a locomotive adhesion receptor which is involved in the transendothelial migration of lymphocytes and the infiltration of lymphocytes into lymphoid or peripheral tissues by binding to VCAM-1 and fibronectin.