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Am J Physiol Heart Circ Physiol (June 3, 2005). doi:10.1152/ajpheart.00153.2005
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Submitted on February 15, 2005
Accepted on June 1, 2005

GRO Family Chemokines are Specialized for Monocyte Arrest from Flow

David F Smith1*, Elena Galkina2, Klaus Ley3, and Yuqing Huo2

1 Department of Molecular Physiology and Biophysics, University of Virginia, Charlottesville, VA, USA
2 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA
3 Department of Molecular Physiology and Biophysics, University of Virginia, Charlottesville, VA, USA; Cardiovascular Research Center, Univeristy of Virginia, Charlottesville, VA, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA

* To whom correspondence should be addressed. E-mail: dfs4j{at}virginia.edu.

Chemokines participate in various processes of monocyte recruitment including monocyte arrest and migration. Our group and others have demonstrated that growth related oncogene (GRO)-{alpha} (CXCL1) could support monocyte arrest in models of inflammation. Here we employed a parallel plate flow chamber and transwell reconstitution assay to test whether GRO family chemokines were sufficient for Mono Mac 6, a human monocytic cell line, and isolated human monocyte recruitment. Our study shows that: (a) GRO-{alpha}, {beta} (CXCL2) and {gamma} (CXCL3) all act as arrest chemokines for monocyte adhesion on vascular cell adhesion molecule (VCAM)-1 under flow in the presence of P-selectin. (b) CXCR2 is the functional receptor for GRO family chemokines in monocyte arrest. However, CXCR2 is not an arrest chemokine receptor in general, since ENA-78 failed to arrest monocytes. (c) GRO-{alpha}, {beta} and {gamma} all fail to raise intracellular free calcium or mediate monocyte chemotaxis. (d) Signaling through G{alpha}i protein, phosphoinositide 3-kinase (PI3K), and actin polymerization, but not calcium mobilization or the mitogen-activated kinases p-38 and MEK, are necessary for GRO-{alpha}-mediated Mono Mac 6 cell arrest under flow. We conclude that the GRO family chemokines are specialized monocyte arrest chemokines. Their role in monocyte recruitment in inflammation can be inhibited by blocking CXCR2 function or downstream signaling events.




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