Details

Autor(en) / Beteiligte

• Turhan, Aslihan
• Weiss, Linnea A.
• Mohandas, Narla
• Coller, Barry S.
• Frenette, Paul S.

Titel

Primary Role for Adherent Leukocytes in Sickle Cell Vascular Occlusion: A New Paradigm

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2002-03, Vol.99 (5), p.3047-3051

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2002

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.