KRDS, a new peptide derived from human lactotransferrin, inhibits platelet aggregation and release reaction

Authors

  • Elisabeth MAZOYER,

    Corresponding author
    1. Institut des Vaisseaux et du Sang, Paris, France
      Correspondence to E. Mazoyer, Institut des Vaisseaux et du Sang, 8 rue Guy Patin, F-75010 Paris, France
    Search for more papers by this author
  • Sylviane LÉVY-TOLEDANO,

    1. Unité 150 de l'Institut National de la Santé et de la Recherche Medicale, et Unité Associée 334 du Centre National de la Recherche Scientifique, Hôpital Lariboisière, Paris, France
    Search for more papers by this author
  • Francine RENDU,

    1. Unité 150 de l'Institut National de la Santé et de la Recherche Medicale, et Unité Associée 334 du Centre National de la Recherche Scientifique, Hôpital Lariboisière, Paris, France
    Search for more papers by this author
  • Laurence HERMANT,

    1. Institut des Vaisseaux et du Sang, Paris, France
    Search for more papers by this author
  • He LU,

    1. Unité 150 de l'Institut National de la Santé et de la Recherche Medicale, et Unité Associée 334 du Centre National de la Recherche Scientifique, Hôpital Lariboisière, Paris, France
    Search for more papers by this author
  • Anne-Marie FIAT,

    1. Laboratoire des Protéines, Unité Associée 1188 du Centre National de la Recherche Scientifique, Université Paris VII, Paris, France
    Search for more papers by this author
  • Pierre JOLLÈS,

    1. Laboratoire des Protéines, Unité Associée 1188 du Centre National de la Recherche Scientifique, Université Paris VII, Paris, France
    Search for more papers by this author
  • Jacques CAEN

    1. Institut des Vaisseaux et du Sang, Paris, France
    Search for more papers by this author

Correspondence to E. Mazoyer, Institut des Vaisseaux et du Sang, 8 rue Guy Patin, F-75010 Paris, France

Abstract

KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested in vitro on human platelet function, and its effects were compared to those of RGDS, a tetrapeptide from human fibrinogen. Both peptides had a high probability of initiating a β-turn and were highly hydrophilic. KRDS inhibited ADP-induced platelet aggregation [median inhibitory concentration (IC50) 350 μM] and fibrinogen binding (IC50 360 μM) to a lesser extent than RGDS (IC50 75 μM and 20 μM, respectively). Different from RGDS, thrombin-induced serotonin release was inhibited by KRDS (750 μM) on normal platelets (55 ± 10%) and type I Glanzmann's thrombasthenia platelets (43%± 1). However, KRDS had no effect on cytoplasmic Ca2+ mobilization, inositol phospholipid metabolism or protein phosphorylation (myosin light chain P20 and P43). In contrast to RGDS, KRDS does not inhibit the binding of monoclonal antibody PAC-1 to activated platelets. KRDS and RGDS inhibited 4β-phorbol-12-myristate-13-acetate (PMA)-induced aggregation and fibrinogen binding, while proteins were normally phosphorylated. Thus, the tetrapeptide KRDS is (a) an inhibitor of serotonin release by a mechanism independent of protein phosphorylation and (b) an inhibitor of fibrinogen binding and, hence, aggregation by a mechanism that may not necessarily involve its direct binding to the glycoprotein IIb-IIIa-complex.

Ancillary