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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1955-1962

RED CELLS

P-selectin mediates the adhesion of sickle erythrocytes to the endothelium

Neil M. Matsui, Lubor Borsig, Steven D. Rosen, Mitra Yaghmai, Ajit Varki, and Stephen H. Embury

From the Departments of Pediatrics and Medicine, San Francisco General Hospital, Departments of Pediatrics, Medicine and Anatomy, University of California, San Francisco, Center for Biomedical Laboratory Sciences, San Francisco State University, and the Northern California Comprehensive Sickle Cell Center, San Francisco; and Glycobiology Research and Training Center, University of California, San Diego, La Jolla.

The adherence of sickle red blood cells (RBCs) to the vascular endothelium may contribute to painful vaso-occlusion in sickle cell disease. Sickle cell adherence involves several receptor-mediated processes and may be potentiated by the up-regulated expression of adhesion molecules on activated endothelial cells. Recent results showed that thrombin rapidly increases the adhesivity of endothelial cells for sickle erythrocytes. The current report presents the first evidence for the novel adhesion of normal and, to a greater extent, sickle RBCs to endothelial P-selectin. Studies of the possible interaction of erythrocytes with P-selectin revealed that either P-selectin blocking monoclonal antibodies or sialyl Lewis tetrasaccharide inhibits the enhanced adherence of normal and sickle cells to thrombin-treated endothelial cells. Both RBC types also adhere to immobilized recombinant P-selectin. Pretreating erythrocytes with sialidase reduces their adherence to activated endothelial cells and to immobilized recombinant P-selectin. Herein the first evidence is presented for the binding of normal or sickle erythrocytes to P-selectin. This novel finding suggests that P-selectin inhibition be considered as a potential approach to therapy for the treatment of painful vaso-occlusion in sickle cell disease.

© 2001 by The American Society of Hematology.
 

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