von Willebrand factor competes with fibrin for occupancy of GPIIb:IIIa on
thrombin-stimulated platelets
RR Hantgan, WL Nichols and ZM Ruggeri
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest
University, Winston-Salem, NC 27103.
We have investigated two major questions related to the molecular basis of
interactions between the three-dimensional fibrin network and
thrombin-stimulated human platelets. First, what are the roles played by
glycoproteins (GP) Ib and IIb:IIIa in linking the fibrin clot tightly to
the platelet surface? Second, does von Willebrand factor (vWF) modulate the
extent of platelet-fibrin interactions? Quantitative fluorescence
microscopy (microfluorimetry) has been used to determine the quantity of
fluorescein-labeled fibrin bound to the surface of thrombin-stimulated,
gel-filtered platelets (the supernatants of which contained small
quantities of vWF) in the presence/absence of receptor- specific and
vWF-specific monoclonal antibodies (MoAbs), as well as exogenous vWF. A
MoAb specific for the GPIIb:IIIa complex exhibited a
concentration-dependent inhibition of fibrin binding, whereas a MoAb
specific for GPIb was ineffective in this regard. Similarly, a MoAb that
recognizes the N-terminal region of vWF involved in GPIb binding did not
influence fibrin binding. In contrast, a MoAb that binds to a C- terminal
region of vWF involved in GPIIb:IIIa recognition caused a specific,
concentration-dependent increase in the quantity of platelet- bound fibrin.
We also found that exogenous vWF caused a concentration- dependent decrease
in fibrin binding. These results support the hypothesis that vWF and
fibrin, both of which are multimeric adhesive ligands, compete for
occupancy of the GPIIb:IIIa complex on thrombin- stimulated platelets.
Volume 75,
Issue 4,
pp. 889-894,
02/15/1990
Copyright © 1990 by The American Society of Hematology
