Two Types of Procoagulant Platelets Are Formed Upon Physiological Activation and Are Controlled by Integrin α IIb β 3

Author:

Topalov Nikolay N.1,Yakimenko Alena O.1,Canault Matthias1,Artemenko Elena O.1,Zakharova Natalia V.1,Abaeva Anastasia A.1,Loosveld Marie1,Ataullakhanov Fazoil I.1,Nurden Alan T.1,Alessi Marie-Christine1,Panteleev Mikhail A.1

Affiliation:

1. From the Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia (N.N.T., E.O.A., N.V.Z., A.A.A., F.I.A., M.A.P.); HemaCore LLC, Moscow, Russia (A.O.Y., F.I.A., M.A.P.); Université de la Méditerranée, Marseille Cedex, France (M.C., M.L., M-C.A.); INSERM Unité Mixte de Recherche, Marseille Cedex, France (M.C., M.L., M-C.A.); Laboratoire d’Hématologie, Hôpital de la Timone, Marseille Cedex, France (M.C., M.L., M-C.A.); National Research Centre for Hematology, Moscow, Russia (F...

Abstract

Objective— Phosphatidylserine (PS) externalization by platelets upon activation is a key event in hemostasis and thrombosis. It is currently believed that strong stimulation of platelets forms 2 subpopulations, only 1 of which expresses PS. Methods and Results— Here, we demonstrate that physiological stimulation leads to the formation of not 1 but 2 types of PS-expressing activated platelets, with dramatically different properties. One subpopulation sustained increased calcium level after activation, whereas another returned to the basal low-calcium state. High-calcium PS-positive platelets had smaller size, high surface density of fibrin(ogen), no active integrin α IIb β 3 , depolarized mitochondrial membranes, gradually lost cytoplasmic membrane integrity, and were poorly aggregated. In contrast, the low-calcium PS-positive platelets had normal size, retained mitochondrial membrane potential and cytoplasmic membrane integrity, and combined retention of fibrin(ogen) with active α IIb β 3 and high proaggregatory function. Formation of low-calcium PS-positive platelets was promoted by platelet concentration increase or shaking and was decreased by integrin α IIb β 3 antagonists, platelet dilution, or in platelets from kindlin-3–deficient and Glanzmann thrombasthenia patients. Conclusion— Identification of a novel PS-expressing platelet subpopulation with low calcium regulated by integrin α IIb β 3 can be important for understanding the mechanisms of PS exposure and thrombus formation.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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