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Originally published online as doi:10.1189/jlb.1105664 on December 18, 2006

Published online before print December 18, 2006
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(Journal of Leukocyte Biology. 2007;81:748-756.)
© 2007 by Society for Leukocyte Biology

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

Kimberly A. Kelly*,1,2, Jennifer R. Allport*,1, Amy M. Yu*, Sumita Sinh{dagger}, E. Helene Sage{ddagger}, Robert E. Gerszten{dagger} and Ralph Weissleder*

* Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA;
{ddagger} Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA; and
{dagger} Department of Cardiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA

2 Correspondence: Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Room 5420, Charlestown, MA 02129, USA. E-mail: kkelly9{at}partners.org

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.

Key Words: adhesion molecules • cell trafficking • phage display




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[Abstract] [Full Text] [PDF]


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