Erythrocyte/endothelial interactions in the pathogenesis of sickle-cell disease: a "real logical" assessment.
Unconvinced that the pathophysiology of sickle-cell disease is fully explained by traditional rheologic considerations, we have searched for additional factors which might be implicated in the development of acute vasocclusive crises in this disease. Sickle RBC adhere abnormally to cultured human vascular endothelial cells, an abnormality requiring neither deoxygenation nor frank morphologic distortion of the RBC. This adherence appears to be caused by an aberrancy of RBC surface charge topography on sickle RBC. Propensity for RBC adherence individual. Among patients with sickle cell anemia, frequency of acute vasocclusive crises correlates significantly with RBC adherence to endothelium. Patients with the clinically less severe doubly heterozygous sickling disorders have a lesser RBC adherence to endothelium than do patients with sickle-cell anemia. RBC/endothelial interactions are modified by factors in the RBC's environment such as fibrinogen, providing a possible mechanism by which concurrent illness might predispose towards the development of vasocclusion. We hypothesize that sickle RBC adherence to endothelium is the factor which initiates acute vasocclusion in sickle-cell disease, either by primarily occluding small vessels or by slowing microvascular blood flow so that secondary, reversible RBC sickling can occur.
D000755:Anemia, Sickle Cell / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000648:ultrastructure; D004913:Erythrocytes, Abnormal / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D012212:Rheology; D012794:Sialic Acids / Q000097:blood; D014471:Umbilical Veins / Q000166:cytology
D012794:Sialic Acids