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Selective induction of a glycoprotein IIIa ligand-induced binding site by
fibrinogen and von Willebrand factor
TH Mondoro, CD Wall, MM White and LK Jennings
Center for Biologics Evaluation and Research, Food and Drug Administration,
Bethesda MD, USA.
Ligand-induced binding sites (LIBS) are neoantigenic regions of
glycoprotein (GP)IIb-IIIa that are exposed upon interaction of the receptor
with the ligand fibrinogen or the ligand recognition sequence (RGDS). LIBS
have been suggested to contribute to postreceptor occupancy events such as
full-scale platelet aggregation, adhesion to collagen, and clot retraction.
This study examined the induction requirements of a GPIIIa LIBS with regard
to ligand specificity. Through the use of the anti-LIBS D3, we report that
this complex- activating antibody induces fibrinogen- and von Willebrand
factor- binding to GPIIb-IIIa on intact platelets. Bound ligand was
detected by flow cytometric analysis and platelet aggregation assays. These
bound ligands increased the number of D3-binding sites and altered the
affinity of D3 for GPIIb-IIIa on platelets. In contrast, activation of
platelet GPIIb-IIIa by D3 did not increase the binding of another RGD-
containing ligand, vitronectin. Furthermore, bound vitronectin on
thrombin-stimulated platelets did not cause the expression of the D3 LIBS
epitope. We conclude direct activation of GPIIb-IIIa in the absence of
platelet activation results in selective ligand interaction and that D3
LIBS induction requires the binding of the multivalent ligands, fibrinogen
or von Willebrand factor. Thus, the region of GPIIIa recognized by D3 may
be an important regulatory domain in ligand- receptor interactions that
directly mediate platelet aggregation.
Volume 88,
Issue 10,
pp. 3824-3830,
11/15/1996
Copyright © 1996 by The American Society of Hematology
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