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PNAS | March 5, 2002 | vol. 99 | no. 5 | 3047-3051
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Medical Sciences
 Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm

Aslihan Turhan*, Linnea A. Weiss*, Narla Mohandasdagger , Barry S. Coller*,Dagger , and Paul S. Frenette*,§

* Department of Medicine, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1079, New York, NY 10029; and dagger  Lawrence Berkeley Laboratory, Berkeley, CA 94720

Edited by Timothy A. Springer, Harvard Medical School, Boston, MA, and approved December 20, 2001 (received for review October 3, 2001)

Vascular occlusion is the major cause of morbidity and mortality in sickle cell disease but its mechanisms are poorly understood. We demonstrate by using intravital microscopy in mice expressing human sickle hemoglobin (SS) that SS red blood cells (RBCs) bind to adherent leukocytes in inflamed venules, producing vasoocclusion of cremasteric venules. SS mice deficient in P- and E-selectins, which display defective leukocyte recruitment to the vessel wall, are protected from vasoocclusion. These data uncover a previously unsuspected paradigm for the pathogenesis of sickle cell vasoocclusion in which adherent leukocytes play a direct role and suggest that drugs targeting SS RBC-leukocyte or leukocyte-endothelial interactions may prevent or treat the vascular complications of this debilitating disease.

Dagger Present address: Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY 10021.

§ To whom reprint requests should be addressed. E-mail: paul.frenette{at}mssm.edu.

www.pnas.org/cgi/doi/10.1073/pnas.052522799
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