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

doi: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

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

Research output: Contribution to journal › Article › peer-review

1742 Citations (Scopus)

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 language	English
Pages (from-to)	577-584
Number of pages	8
Journal	Cell
Volume	60
Issue number	4
DOIs	https://doi.org/10.1016/0092-8674(90)90661-W
Publication status	Published - Feb 23 1990
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/0092-8674(90)90661-W

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@article{63f948cd200940c4abfe0ceaddb3736a,

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

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.",

author = "Elices, {Mariano J.} and Laurelee Osborn and Yoshikazu Takada and Carol Crouse and Stefan Luhowskyj and Hemler, {Martin E.} and Lobb, {Roy R.}",

note = "Funding Information: We thank Drs. T Albino, C. Damsky, M. Ginsberg, J. Harlan, F. Sanchez-Madrid, S. Santoso, T. Springer, E. Wayner. and G. Yeh for providing antibodies used in this study. M. J. E. is a fellow of the Cancer Research Institute (New York). This work was supported in part by National Institutes of Health grant GM33903 (M. E. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked hdveftisemenf” in accordance solely to indicate this fact.",

year = "1990",

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doi = "10.1016/0092-8674(90)90661-W",

language = "English",

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pages = "577--584",

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T1 - VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site

AU - Elices, Mariano J.

AU - Osborn, Laurelee

AU - Takada, Yoshikazu

AU - Crouse, Carol

AU - Luhowskyj, Stefan

AU - Hemler, Martin E.

AU - Lobb, Roy R.

N1 - Funding Information: We thank Drs. T Albino, C. Damsky, M. Ginsberg, J. Harlan, F. Sanchez-Madrid, S. Santoso, T. Springer, E. Wayner. and G. Yeh for providing antibodies used in this study. M. J. E. is a fellow of the Cancer Research Institute (New York). This work was supported in part by National Institutes of Health grant GM33903 (M. E. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked hdveftisemenf” in accordance solely to indicate this fact.

PY - 1990/2/23

Y1 - 1990/2/23

N2 - 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.

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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JF - Cell

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

Abstract

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