SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration

SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration

VCAM‐1 is a cell surface molecule, which has been shown to mediate leukocyte adhesion to the endothelium and subsequent transmigration. Although VCAM‐1 regulates adhesion through its interaction with VLA‐4, VLA‐4 does not play a role in VCAM‐1‐dependent diapedesis, an observation suggesting the pres...

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Bibliographic Details
Published in:Journal of leukocyte biology Vol. 81; no. 3; pp. 748 - 756
Main Authors: Kelly, Kimberly A., Allport, Jennifer R., Yu, Amy M., Sinh, Sumita, Sage, E. Helene, Gerszten, Robert E., Weissleder, Ralph
Format: Journal Article
Language:English
Published: United States Society for Leukocyte Biology 01-03-2007
Subjects:
Actins - physiology
adhesion molecules
Animals
Cell Movement - genetics
Cell Movement - physiology
cell trafficking
Cytoskeleton - physiology
Female
Humans
Intercellular Junctions - physiology
Leukocytes - physiology
Ligands
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteonectin - deficiency
Osteonectin - genetics
Osteonectin - metabolism
phage display
Protein Binding
Structure-Activity Relationship
Vascular Cell Adhesion Molecule-1 - metabolism
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Summary:VCAM‐1 is a cell surface molecule, which has been shown to mediate leukocyte adhesion to the endothelium and subsequent transmigration. Although VCAM‐1 regulates adhesion through its interaction with VLA‐4, VLA‐4 does not play a role in VCAM‐1‐dependent diapedesis, an observation suggesting the presence of a second ligand for VCAM‐1. We now report a novel interaction between VCAM‐1 and secreted protein acidic and rich in cysteine (SPARC), which induces actin cytoskeletal rearrangement and intercellular gaps, physiological processes known to be important for leukocyte transmigration. The binding of leukocyte‐derived SPARC to VCAM‐1 was demonstrated to be necessary for leukocyte transmigration through endothelial monolayers (diapedesis) in vitro, and furthermore, SPARC null mice have abnormalities in leukocyte recruitment to the inflamed peritoneum in vivo. These findings provide new insight into the mechanisms of transendothelial leukocyte migration and suggest a potential, targetable interaction for therapeutic intervention.
Bibliography:These authors contributed equally to this work.
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ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.1105664