VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site

Mariano J. Elices, Laurelee Osborn, Yoshikazu Takada, Carol Crouse, Stefan Luhowskyj, Martin E. Hemler, Roy R. Lobb

Research output: Contribution to journalArticle

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Abstract

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 α4 subunit cDNA) resulted in specific cell adhesion to VCAM-1, and anti VLM4 antibodies completely inhibited VCAM-1-dependent cell-cell attachment. In addition, VLA-4 expression allowed K562 cells to attach to the heparin 11 binding region (FN-40) of fibronectin. However, VLA-41VCAM-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 FN40. The VCAM-1/VLA-4 ligand-receptor pair may play a major role in the recruitment of mononuclear leukocytes to inflammatory sites in vivo.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalCell
Volume60
Issue number4
DOIs
Publication statusPublished - Feb 23 1990
Externally publishedYes

Fingerprint

Integrin alpha4beta1
Vascular Cell Adhesion Molecule-1
Fibronectins
Integrins
Endothelium
Leukocytes
Binding Sites
Integrin alpha1beta1
Mononuclear Leukocytes
Lymphocytes
K562 Cells
Cell adhesion
Endothelial cells
Cell Adhesion
Transfection
Heparin
Anti-Idiotypic Antibodies
Endothelial Cells
Complementary DNA
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Elices, M. J., Osborn, L., Takada, Y., Crouse, C., Luhowskyj, S., Hemler, M. E., & Lobb, R. R. (1990). VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site. Cell, 60(4), 577-584. https://doi.org/10.1016/0092-8674(90)90661-W

VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site. / Elices, Mariano J.; Osborn, Laurelee; Takada, Yoshikazu; Crouse, Carol; Luhowskyj, Stefan; Hemler, Martin E.; Lobb, Roy R.

In: Cell, Vol. 60, No. 4, 23.02.1990, p. 577-584.

Research output: Contribution to journalArticle

Elices, MJ, Osborn, L, Takada, Y, Crouse, C, Luhowskyj, S, Hemler, ME & Lobb, RR 1990, 'VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site', Cell, vol. 60, no. 4, pp. 577-584. https://doi.org/10.1016/0092-8674(90)90661-W
Elices, Mariano J. ; Osborn, Laurelee ; Takada, Yoshikazu ; Crouse, Carol ; Luhowskyj, Stefan ; Hemler, Martin E. ; Lobb, Roy R. / VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site. In: Cell. 1990 ; Vol. 60, No. 4. pp. 577-584.
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AB - 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 α4 subunit cDNA) resulted in specific cell adhesion to VCAM-1, and anti VLM4 antibodies completely inhibited VCAM-1-dependent cell-cell attachment. In addition, VLA-4 expression allowed K562 cells to attach to the heparin 11 binding region (FN-40) of fibronectin. However, VLA-41VCAM-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 FN40. The VCAM-1/VLA-4 ligand-receptor pair may play a major role in the recruitment of mononuclear leukocytes to inflammatory sites in vivo.

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