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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.
Previous Article | Next Article 
Submitted July 12, 2004
Accepted December 7, 2004
Endothelial expression of E-selectin is induced by the platelet specific chemokine Platelet Factor 4 through LRP in an NF- B dependent manner
Guangyao Yu, Ann H Rux, Peihong Ma, Khalil Bdeir, and Bruce S Sachais*
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
* Corresponding author; email: sachais{at}mail.med.upenn.edu.
The involvement of platelets in the pathogenesis of atherosclerosis has recently gained much attention. Platelet factor 4 (PF4), a platelet specific chemokine released upon 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 NF- B is critical for PF4 induced E-selectin expression, as demonstrated by promoter activation studies and electrophoretic mobility shift assay. Further, we have identified the low density lipoprotein receptor-related protein (LRP) 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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