Selective triggering of platelet apoptosis, platelet activation or both

Summary 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 mimeti...

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Bibliographic Details
Published in:British journal of haematology 2013-04, Vol.161 (2), p.245-254
Main Authors: Gyulkhandanyan, Armen V., Mutlu, Asuman, Freedman, John, Leytin, Valery
Format: Article
Language:English
Subjects:
ABT‐737 and thrombin
Apoptosis - drug effects
Biological and medical sciences
Biphenyl Compounds - pharmacology
Blood Platelets - metabolism
Ca2+‐ionophore A23187
Calcimycin - pharmacology
Calcium Ionophores - pharmacology
Female
Hematologic and hematopoietic diseases
Hemostatics - pharmacology
Hot Temperature
Humans
Male
Medical sciences
Membrane Potential, Mitochondrial - drug effects
mitochondrial membrane depolarization
Nitrophenols - pharmacology
P-Selectin - metabolism
Piperazines - pharmacology
Platelet Activation - drug effects
platelet apoptosis and activation
P‐selectin exposure
Sulfonamides - pharmacology
Thrombin - pharmacology
Time Factors
Tumors
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Summary:Summary 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 (ΔΨm) depolarization and activation as P‐selectin exposure. At optimal treatment conditions (90–180 min, 37°C), ABT‐737 predominantly induced apoptosis, when 77–81% platelets undergo only ΔΨm depolarization. The ABT‐737 impact on ΔΨm depolarization is strongly time‐ and temperature‐dependent, and much higher at 37°C than at room temperature. In contrast, when platelets were treated with thrombin for 15–90 min at either temperature, activation‐only was predominantly (79–85%) induced, whereas A23187 triggers both apoptosis and activation (73–81%) when platelets were treated for 15–60 min at 37°C or 15–90 min at room temperature. These data demonstrate that, depending on the triggering stimulus, platelets predominantly undergo ΔΨm 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.
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.12237