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© 2000 American Heart Association, Inc.
Clinical Research |
The Stromal Cell–Derived Factor-1 Chemokine Is a Potent Platelet Agonist Highly Expressed in Atherosclerotic Plaques
From the Department of Medicine, Massachusetts General Hospital (S.A.-Y., A.S., A.D.L.) and Brigham and Women’s Hospital (F.M., G.K.S., P.L.), Harvard Medical School, Boston, Mass.
Correspondence to Andrew D. Luster, Massachusetts General Hospital-East, Building 149, 13th St, Charlestown, MA 02129. E-mail luster{at}helix.mgh.harvard.edu
Abstract—Chemokines are
chemotactic cytokines that activate and direct the
migration of leukocytes. However, their role in modulating platelet
function has not been shown. We studied the direct effect of chemokines
on human platelets and found that of the 16 tested only stromal
cell–derived factor (SDF)-1 induced platelet aggregation,
accompanied by a rise in intracellular calcium. Platelets expressed
the SDF-1 receptor, CXCR4, and an antibody to CXCR4 and pertussis toxin
inhibited SDF-1–induced platelet aggregation, confirming that this
effect is mediated through CXCR4, a G
i-coupled receptor.
SDF-1–induced platelet aggregation was also inhibited by
wortmannin, LY294002, and genistein, suggesting that
phosphatidylinositol 3–kinase and tyrosine kinase are likely involved
in SDF-1–induced platelet aggregation. Because chemokines are
produced from multiple vascular cells and atherosclerotic vessels are
prone to develop platelet-rich thrombi, we examined the expression
of SDF-1 in human atheroma. SDF-1 protein was highly
expressed in smooth muscle cells, endothelial cells,
and macrophages in human atherosclerotic plaques but not in
normal vessels. Our studies demonstrate a direct effect of a chemokine
in inducing platelet activation and suggest a role for SDF-1 in the
pathogenesis of atherosclerosis and
thrombo-occlusive diseases.
Key Words: stromal cell–derived factor-1 • chemokine • platelet • atherosclerosis
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