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.

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.

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: Nikolay N Topalov, Alena O Yakimenko, Matthias Canault, Elena O Artemenko, Natalia V Zakharova, Anastasia A Abaeva, Marie Loosveld, Fazoil I Ataullakhanov, Alan T Nurden, Marie-Christine Alessi, Mikhail A Panteleev
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 32 Issue 10 Pg. 2475-83 (Oct 2012) ISSN: 1524-4636 [Electronic] United States
• PMID: 22837472 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FERMT3 protein, human
• Membrane Proteins
• Neoplasm Proteins
• Phosphatidylserines
• Platelet Glycoprotein GPIIb-IIIa Complex
• Calcium

Topics

• Blood Coagulation (physiology)
• Blood Platelets (pathology, physiology)
• Calcium (metabolism)
• Humans
• Membrane Potential, Mitochondrial (physiology)
• Membrane Proteins (deficiency)
• Neoplasm Proteins (deficiency)
• Phosphatidylserines (metabolism)
• Platelet Glycoprotein GPIIb-IIIa Complex (physiology)
• Thrombasthenia (pathology, physiopathology)
• Thrombosis (physiopathology)