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

Takaaki Hato; Akito Watanabe; Shingo Nakatani; Yoko Minamoto; Shigeru Fujita

doi:10.1055/s-0038-1653739

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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

¹The Blood Transfusion Division, Ehime University School of Medicine, Ehime, Japan

,

Akito Watanabe

²The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan

,

Shingo Nakatani

²The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan

,

Yoko Minamoto

²The Department of Internal Medicine I, Ehime University School of Medicine, Ehime, Japan

,

Shigeru Fujita

²The 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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A Novel Mechanism for Exposure of Fibrinogen Binding Sites on GPIIb-IIIa by a Monoclonal Antibody

Publication History

Summary

References