title: Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin.
abstract: The adhesion of sickle erythrocytes to vascular endothelium is important to the generation of vascular occlusion. Interactions between sickle cells and the endothelium use 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 uses P-selectin and that this component of 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.
authors.affiliation: Department of Pediatrics, University of California-San Francisco, San Francisco General Hospital, and the Northern California Comprehensive Sickle Cell Center, San Francisco 94110, USA.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Matsui
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Embury
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004913:Erythrocytes, Abnormal / Q000473:pathology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D019007:P-Selectin / Q000378:metabolism* / Q000502:physiology; D010477:Perfusion; D011485:Protein Binding / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D019007:P-Selectin; D006493:Heparin; D013917:Thrombin