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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-02-0626.
Submitted March 6, 2002
Accepted June 26, 2002
Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin
Neil M Matsui, Ajit Varki, and Stephen H Embury*
Department of Pediatrics, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA; Northern California Comprehensive Sickle Cell Center, San Francisco, CA, USA
Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA, USA
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA
* Corresponding author; email: sembury{at}itsa.ucsf.edu.
The adhesion of sickle erythrocytes to vascular endothelium is important to the generation of vascular occlusion. Interactions between sickle cells and the endothelium employs several cell adhesion molecules. We have reported that sickle cell adhesion to endothelial cells under static conditions involves P-selectin. Others have shown that sickle cell adhesion is decreased by unfractionated heparin, but the molecular target of this inhibition has not been defined. We postulated that the adhesion of sickle cells to P-selectin might be the pathway blocked by unfractionated heparin. In this report we demonstrate that the flow adherence of sickle cells to thrombin treated human vascular endothelial cells also employs P-selectin and that this adhesion is inhibited by unfractionated heparin. We also demonstrate that sickle cells adhere to immobilized recombinant P-selectin under flow conditions. This adhesion too was inhibited by unfractionated heparin, in a concentration range that is clinically attainable. These findings and the general role of P-selectin in initiating adhesion of blood cells to the endothelium suggest that unfractionated heparin may be useful in preventing painful vascular occlusion. A clinical trial to test this hypothesis is indicated.
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