VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site.
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.
Elices
M J
MJ
Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Osborn
L
L
Takada
Y
Y
Crouse
C
C
Luhowskyj
S
S
Hemler
M E
ME
Lobb
R R
RR
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000502:physiology*; D010957:Plasmids; D011247:Pregnancy; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000378:metabolism*; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D014162:Transfection; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D004247:DNA