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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3545-3551.
Prepublished online as a Blood First Edition Paper on December 9, 2004; DOI 10.1182/blood-2004-07-2617.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-{kappa}B–dependent manner

Guangyao Yu, Ann H. Rux, Peihong Ma, Khalil Bdeir, and Bruce S. Sachais

From the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.

The involvement of platelets in the pathogenesis of atherosclerosis has recently gained much attention. Platelet factor 4 (PF4), a platelet-specific chemokine released on platelet activation, has been localized to atherosclerotic lesions, including macrophages and endothelium. In this report, we demonstrate that E-selectin, an adhesion molecule involved in atherogenesis, is up-regulated in human umbilical vein endothelial cells exposed to PF4. Induction of E-selectin RNA is time and dose dependent. Surface expression of E-selectin, as measured by flow cytometry, is also increased by PF4. PF4 induces E-selectin expression by activation of transcriptional activity. Activation of nuclear factor-{kappa}B is critical for PF4-induced E-selectin expression, as demonstrated by promoter activation studies and electrophoretic mobility shift assays. Further, we have identified the low-density lipoprotein receptor-related protein as the cell surface receptor mediating this effect. These results demonstrate that PF4 is able to increase expression of E-selectin by endothelial cells and represents another potential mechanism by which platelets may participate in atherosclerotic lesion progression.


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