title: Two types of procoagulant platelets are formed upon physiological activation and are controlled by integrin α(IIb)β(3).
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia.
authors: Nikolay N
authors: NN
authors: Topalov
authors: Alena O
authors: AO
authors: Yakimenko
authors: Matthias
authors: M
authors: Canault
authors: Elena O
authors: EO
authors: Artemenko
authors: Natalia V
authors: NV
authors: Zakharova
authors: Anastasia A
authors: AA
authors: Abaeva
authors: Marie
authors: M
authors: Loosveld
authors: Fazoil I
authors: FI
authors: Ataullakhanov
authors: Alan T
authors: AT
authors: Nurden
authors: Marie-Christine
authors: MC
authors: Alessi
authors: Mikhail A
authors: MA
authors: Panteleev
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency; D009363:Neoplasm Proteins / Q000172:deficiency; D010718:Phosphatidylserines / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*; D013915:Thrombasthenia / Q000473:pathology / Q000503:physiopathology*; D013927:Thrombosis / Q000503:physiopathology
chemical_list: C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010718:Phosphatidylserines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D002118:Calcium