title: Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm.
abstract: 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.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1079, New York, NY 10029, USA.
authors.forename: Aslihan
authors.initials: A
authors.lastname: Turhan
authors.forename: Linnea A
authors.initials: LA
authors.lastname: Weiss
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Barry S
authors.initials: BS
authors.lastname: Coller
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000502:physiology; D006451:Hemoglobin, Sickle / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014652:Vascular Diseases / Q000517:prevention & control*
chemical_list: D006451:Hemoglobin, Sickle