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

First Author  Kelly KA Year  2007
Journal  J Leukoc Biol Volume  81
Issue  3 Pages  748-56
PubMed ID  17178915 Mgi Jnum  J:118613
Mgi Id  MGI:3699976 Doi  10.1189/jlb.1105664
Citation  Kelly KA, et al. (2007) SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration. J Leukoc Biol 81(3):748-56
abstractText  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.
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