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Inhibition of sickle erythrocyte adhesion to immobilized thrombospondin by
von Willebrand factor under dynamic flow conditions
GA Barabino, RJ Wise, VA Woodbury, B Zhang, KA Bridges, RP Hebbel, J Lawler and BM Ewenstein
Department of Chemical Engineering, Northeastern University, Boston, MA
02115, USA.
Sickle red blood cell (RBC) adhesion to the blood vessel wall is
hypothesized to be the initiating event in the periodic vaso-occlusive
episodes that characterize sickle cell disease (SCD). Thrombospondin-1
(TSP) and von Willebrand factor (vWF) have each been implicated in the
adhesion of sickle RBC to vascular endothelial cells (EC) and
subendothelial matrices. To better understand the contributions of each of
these adhesive glycoproteins, we examined the adhesion of sickle RBC to
immobilized TSP and vWF using a parallel plate flow chamber. Under
postcapillary venular shear stress (1 dyne/cm2), sickle RBC adhered
preferentially to TSP. To explore potential interactive effects of vWF and
TSP, we examined sickle RBC adhesion to mixtures of these proteins. Whether
the proteins were first combined in solution or sequentially applied to the
slide, the presence of vWF inhibited the binding of sickle RBC to TSP. The
inhibition of adhesion by vWF was shown to be the result of specific and
saturable binding of vWF to TSP. Furthermore, vWF in solution at normal
plasma levels also inhibited RBC adhesion to immobilized TSP. These data
indicate that sickle RBC adhesion in vivo may be significantly influenced
by the relative concentrations of TSP and vWF in the vascular wall.
Volume 89,
Issue 7,
pp. 2560-2567,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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