Fibronectin and von Willebrand factor mediated sickle erythrocyte adhesion to human endothelial cells under venous flow conditions
Wick, Timothy Michael
McIntire, Larry V.
Doctor of Philosophy
Sickle erythrocytes have previously been demonstrated to be abnormally adhesive to human endothelial cells in both static incubation assays and under venous flow conditions. The extent to which human fibronectin and human von Willebrand factor (vWF) can promote sickle erythrocyte adhesion to human endothelial cells was studied under venous flow conditions in a parallel-plate laminar flow chamber (wall shear stress = 1.0 dyne/cm$\sp2$). The data presented indicate that endothelial cell derived, unusually large, vWF multimers are optimally effective at promoting receptor-mediated sickle erythrocyte adhesion to endothelial cells. vWF appears to bind to erythrocyte surfaces via receptors immunologically identical to the glycoprotein Ib and glycoprotein IIb/IIIa receptors on platelet surfaces. Other cytoadhesive plasma proteins, such as fibronectin and purified plasma vWF multimers, can also promote sickle red cell adhesion to endothelial cells, but to a much lesser extent. Unusually large vWF multimers are also able to mediate the adhesion of young non-sickle red blood cells to endothelial cells. These results indicate that red cell adhesion to endothelial cells is due to an increase in the fraction of light, young erythrocytes in sickle blood and not necessarily to the presence of sickle hemoglobin. Vaso-occlusive crises in sickle cell anemia may be caused, at least in part, by adhesive interactions between the abnormal surfaces of sickle red blood cells and the endothelium after release of unusually large vWF multimeric forms from stimulated or damaged endothelial cells.
Biomedical engineering; Biophysics