Inhibition of Platelet Adhesion to Fibrin(ogen) in Flowing Whole Blood by Arg-Gly-Asp and Fibrinogen γ-Chain Carboxy Terminal Peptides

Roy R Hantgan; Silvia C Endenburg; I Cavero; Gérard Marguerie; André Uzan; Jan J Sixma; Philip G de Groot

doi:10.1055/s-0038-1646346

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 68(06): 694-700
DOI: 10.1055/s-0038-1646346

Original Article

Schattauer GmbH Stuttgart

Inhibition of Platelet Adhesion to Fibrin(ogen) in Flowing Whole Blood by Arg-Gly-Asp and Fibrinogen γ-Chain Carboxy Terminal Peptides

Authors

Roy R Hantgan

¹The Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC, USA
Silvia C Endenburg

²The Department of Haematology, University of Utrecht, Utrecht, The Netherlands
I Cavero

³The Rhône-Poulenc Rorer R-D, Vitry sur Seine, France
Gérard Marguerie

⁴The Laboratoire d’Hématologie, INSERM U127, Grenoble, France
André Uzan

³The Rhône-Poulenc Rorer R-D, Vitry sur Seine, France
Jan J Sixma

²The Department of Haematology, University of Utrecht, Utrecht, The Netherlands
Philip G de Groot

²The Department of Haematology, University of Utrecht, Utrecht, The Netherlands

Abstract

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Summary

We have employed synthetic peptides with sequences corresponding to the integrin receptor-recognition regions of fibrinogen as inhibitors of platelet aggregation and adhesion to fibrinogen-and fibrin-coated surfaces in flowing whole blood, using a rectangular perfusion chamber at wall shear rates of 300 s^–1 and 1,300 s^–1. D-RGDW caused substantial inhibition of platelet aggregation and adhesion to fibrinogen and fibrin at both shear rates, although it was least effective at blocking platelet adhesion to fibrin at 300 s^–1. RGDS was a weaker inhibitor, and produced a biphasic dose-response curve; SDRG was inactive. HHLGGAK-QAGDV partially inhibited platelet aggregation and adhesion to fibrin(ogen) at both shear rates. These results support the identification of an RGD-specific receptor, most likely the platelet integrin glycoprotein IIb: III a, as the primary receptor responsible for platelet: fibrin(ogen) adhesive interactions under flow conditions, and indicate that platelet adhesion to surface bound fibrin(ogen) is stabilized by multivalent receptor-ligand contacts.

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References

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