Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 161, Issue 2, Pages 245-254Publisher
WILEY
DOI: 10.1111/bjh.12237
Keywords
platelet apoptosis and activation; mitochondrial membrane depolarization; P-selectin exposure; ABT-737 and thrombin; Ca2+-ionophore A23187
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Funding
- Heart and Stroke Foundation of Ontario, Canada
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Anucleate platelets perform two fundamental processes, activation and apoptosis. We elaborated an approach for selective and concurrent stimulation of platelet apoptosis and/or activation, processes important in haemostasis and platelet clearance. Human platelets were treated with BH3 mimetic ABT-737, thrombin, calcium ionophore A23187 and matched diluents. Apoptosis was determined as mitochondrial inner membrane potential (m) depolarization and activation as P-selectin exposure. At optimal treatment conditions (90180min, 37 degrees C), ABT-737 predominantly induced apoptosis, when 7781% platelets undergo only m depolarization. The ABT-737 impact on m depolarization is strongly time- and temperature-dependent, and much higher at 37 degrees C than at room temperature. In contrast, when platelets were treated with thrombin for 1590min at either temperature, activation-only was predominantly (7985%) induced, whereas A23187 triggers both apoptosis and activation (7381%) when platelets were treated for 1560min at 37 degrees C or 1590min at room temperature. These data demonstrate that, depending on the triggering stimulus, platelets predominantly undergo m depolarization-only, P-selectin exposure-only, or both responses, indicating that platelet apoptosis and activation are different phenomena driven by different mechanisms. The described model provides a basis for studying differential pharmacological manipulation of platelet apoptosis and activation and their role in haemostasis, thrombosis and platelet clearance.
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