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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

Roy R Hantgan
1   The Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC, USA
,
Silvia C Endenburg
2   The Department of Haematology, University of Utrecht, Utrecht, The Netherlands
,
I Cavero
3   The Rhône-Poulenc Rorer R-D, Vitry sur Seine, France
,
Gérard Marguerie
4   The Laboratoire d’Hématologie, INSERM U127, Grenoble, France
,
André Uzan
3   The Rhône-Poulenc Rorer R-D, Vitry sur Seine, France
,
Jan J Sixma
2   The Department of Haematology, University of Utrecht, Utrecht, The Netherlands
,
Philip G de Groot
2   The Department of Haematology, University of Utrecht, Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 08 November 1991

Accepted after revision 17 July 1992

Publication Date:
04 July 2018 (online)

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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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