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

• Published in: The Journal of biological chemistry 1993-11, Vol.268 (33), p.24655-24664
• Main Authors: Chan, P Y, Aruffo, A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Cell Adhesion - drug effects; Cell Adhesion Molecules - metabolism; Cell Line, Transformed; Chemotaxis, Leukocyte; DNA Primers; Extracellular Matrix - metabolism; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Ligands; Lymphocytes - cytology; Lymphocytes - metabolism; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Membranes, Artificial; Molecular Sequence Data; Phytohemagglutinins - pharmacology; Polycarboxylate Cement; Receptors, Fc - metabolism; Receptors, Very Late Antigen - physiology; Recombinant Fusion Proteins - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Vascular Cell Adhesion Molecule-1
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)74516-5

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.