Neutralization of the Antiheparin Activity of Platelet Factor 4 by a Monoclonal Antibody

Leopoldo Saggin; Flavia Cazzola; Giuseppe Corona; Emanuela Salvatico; Giuseppe Cella; Marco Prosdocimi

doi:10.1055/s-0038-1648395

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 67(01): 137-143
DOI: 10.1055/s-0038-1648395

Original Articles

Schattauer GmbH Stuttgart

Neutralization of the Antiheparin Activity of Platelet Factor 4 by a Monoclonal Antibody

Authors

Leopoldo Saggin

¹The Dept. of Vascular Biology, FIDIA S.p.A., Abano Terme, Italy
Flavia Cazzola

²Advanced Technology Division , FIDIA S.p.A., Abano Terme, Italy
Giuseppe Corona

²Advanced Technology Division , FIDIA S.p.A., Abano Terme, Italy
Emanuela Salvatico

¹The Dept. of Vascular Biology, FIDIA S.p.A., Abano Terme, Italy
Giuseppe Cella

³II Chair of Medicine, Institute of Medical Semeiotics, University of Padua, Padua, ltaly
Marco Prosdocimi

¹The Dept. of Vascular Biology, FIDIA S.p.A., Abano Terme, Italy

Abstract

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Summary

We have produced a panel of monoclonal antibodies (mAbs) against rabbit platelet factor 4 (PF4). Two of these mAbs have been characterized in this study. In particular the antibody called 10B2, which also recognizes the human molecule, is able to block PF4’s ability to neutralize heparin in a modified Heparin-Factor Xa chromogenic assay. The inhibition appears to be more than 95% at 1:1 mAb/PF4 molar ratio both for purified rabbit and human PF4. Similar results were obtained using supernatants from stimulated human platelets (90% of inhibition at 1:1 mAb/ PF4 molar ratio) or using Fab fragments from 10B2. Studies to determine the antigenic determinant against which 10B2 is directed, show that this is an assembled epitope which involves disulfide bonds of the PF4.

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References

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