Recombinant P-selectin glycoprotein-ligand-1 delays thrombin-induced platelet aggregation: a new role for P-selectin in early aggregation.

British Journal of Pharmacology
Jean-François ThéorêtYahye Merhi

Abstract

1. P-selectin is involved, with P-selectin glycoprotein (GP)-ligand-1 (PSGL-1), in platelet/leukocyte interactions during thrombo-inflammatory reactions; it also stabilizes platelet aggregates. Its antagonism accelerates thrombolysis and enhances the anti-aggregatory effects of GPIIb-IIIa inhibitors. This study was designed to investigate the mechanisms of P-selectin-mediated platelet aggregation. 2. In freshly isolated human platelets, P-selectin translocation after thrombin stimulation increased rapidly to 48, 72, and 86% positive platelets after 60, 120, and 300 s, respectively. Platelet aggregation at 60 s post-stimulation averaged 46.7 +/- 1.9% and its extent followed closely the kinetics of P-selectin translocation. 3. Pre-treatment of platelets with P-selectin antagonists, a recombinant PSGL-1 (rPSGL-Ig) or a blocking monoclonal antibody, significantly delayed platelet aggregation in a dose-dependent manner. At 100 microg ml(-1) of rPSGL-Ig, platelet aggregation was completely inhibited up to 60 s post-stimulation and increased thereafter to reach maximal aggregation at 5 min. The second phase of platelet aggregation, in the presence of rPSGL-Ig, was completely prevented by the addition of a GPIIb-IIIa antagonist (Reopro...Continue Reading

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Citations

Dec 16, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·C ZhangJ W Kupiec-Weglinski
Jun 10, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Letícia Gonçalves FreitasLuci Maria SantAna Dusse
Aug 20, 2009·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Eman MosadAzza A Eltayeb
Jul 15, 2009·Immunological Reviews·Douglas A CarlowHermann J Ziltener
Jul 9, 2010·Expert Opinion on Therapeutic Targets·Thilo HackertJens Werner
Jun 3, 2008·British Journal of Haematology·Simon F De MeyerHans Deckmyn
May 24, 2011·Thrombosis Research·Jean-François ThéorêtYahye Merhi

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