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Thromb Haemost 1996; 76(06): 1030-1037
DOI: 10.1055/s-0038-1650703
Original Article
Schattauer GmbH Stuttgart

Differential Inhibition of Fibrinogen Binding to Agonist-and RGDS Peptide-activated States of GPIIb-IIIa by an anti-GPIIIa Monoclonal Antibody, PMA5

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

Publication History

Received 27 February 1996

Accepted after revision 05 August 1996

Publication Date:
21 August 2018 (online)

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Summary

Platelet agonists and RGD-containing peptides can convert platelet membrane glycoprotein (GP) Ilb-IIIa from its resting state to an activated state competent to bind soluble fibrinogen. We examined the effects of two anti-GPIIb-IIIa monoclonal antibodies, PMA1 and PMA5, on fibrinogen binding to agonist- and RGD-activated GPIIb-IIIa. PMA1 abolished aggregation of both agonist- and RGDS peptide-activated fixed platelets, and inhibited the binding of 125I-fibrinogen to these platelets almost completely. PMA5 had the same effects on agonist-activated platelets, but had little effect on the aggregation of RGDS-activated fixed platelets, and inhibited fibrinogen binding to RGDS-activated fixed platelets by only 44%. PMA5 bound to agonist- and RGDS-activated platelets equally. Immunoblot analysis showed that PMA5 bound to intact GPIIIa, but not to a 66 kDa fragment of GPIIIa digested by chymotrypsin. Although PMA5 inhibited platelet adhesion to immobilized fibrinogen by 94%, 44% of the remaining adherent platelets were spread. In contrast, no platelet spreading was observed in the presence of PMA1. These findings indicate that PMA5 is a novel anti-GPIIIa monoclonal antibody with the ability to inhibit fibrinogen binding to agonist- and RGD-activated states of GPIIb-IIIa differentially, and suggest that binding of immobilized fibrinogen to RGD-activated GPIIb-IIIa is necessary for platelet spreading.

 

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