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Thromb Haemost 1995; 73(01): 138-143
DOI: 10.1055/s-0038-1653739
Original Article
Platelets
Schattauer GmbH Stuttgart

A Novel Mechanism for Exposure of Fibrinogen Binding Sites on GPIIb-IIIa by a Monoclonal Antibody

Takaaki Hato
1   The Blood Transfusion Division, Ehime University School of Medicine, Ehime, Japan
,
Akito Watanabe
2   The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan
,
Shingo Nakatani
2   The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan
,
Yoko Minamoto
2   The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan
,
Shigeru Fujita
2   The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan
› Author Affiliations
Further Information

Publication History

Received 04 July 1994

Accepted after revision 09 September 1994

Publication Date:
09 July 2018 (online)

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Summary

Conformational changes in platelet membrane glycoprotein (GP) IIb-IIIa, whose nature is not defined, lead to exposure of fibrinogen binding sites. We have reported previously that F(ab’)2fragments of a monoclonal antibody, PMA4, directed against the GPIIb-IIIa complex- specific domain, induced binding of fibrinogen to platelets without causing intracellular activation, whereas Fab did not. In this study, we examined the mechanism responsible for the difference in the ability of PMA4 F(ab’)2and Fab to expose fibrinogen binding sites. PMA4 Fab had affinity for GPIIb-IIIa similar to that of PMA4 F(ab’)2. Addition of F(ab’)2goat anti-mouse Fab antibody to cross-link PMA4 Fab-bound GPIIb-IIIa molecules induced fibrinogen binding. There was a direct correlation between the number of molecules of PMA4 F(ab’)2and the amount of fibrinogen bound. PMA4 did not recognize ligand-induced binding sites (LIBS). These results suggest that the cross-linking of special sites on the GPIIb-IIIa complex-specific domain by bivalent antibody alters the conformation of GPIIb-IIIa to a state competent to bind soluble fibrinogen and that conformational changes in non-LIBS are involved in the mechanism for exposing fibrinogen binding sites on GPIIb-IIIa.

 

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