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 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.
Chan
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Department of Cellular Interactions, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
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D000595:Amino Acid Sequence; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002461:Cell Line, Transformed; D002634:Chemotaxis, Leukocyte; D017931:DNA Primers; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D011076:Polycarboxylate Cement; D011961:Receptors, Fc / Q000378:metabolism; D016029:Receptors, Very Late Antigen / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D005353:Fibronectins; D008024:Ligands; D008567:Membranes, Artificial; D010835:Phytohemagglutinins; D011076:Polycarboxylate Cement; D011961:Receptors, Fc; D016029:Receptors, Very Late Antigen; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1; C005506:polycarbonate; D013755:Tetradecanoylphorbol Acetate