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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.

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