title: Selective triggering of platelet apoptosis, platelet activation or both.
abstract: 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.
authors: Division of Transfusion Medicine, Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada.
authors: Armen V
authors: AV
authors: Gyulkhandanyan
authors: Asuman
authors: A
authors: Mutlu
authors: John
authors: J
authors: Freedman
authors: Valery
authors: V
authors: Leytin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D061207:Calcium Ionophores / Q000494:pharmacology*; D005260:Female; D006490:Hemostatics / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009596:Nitrophenols / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C501332:ABT-737; D001713:Biphenyl Compounds; D061207:Calcium Ionophores; D006490:Hemostatics; D009596:Nitrophenols; D019007:P-Selectin; D010879:Piperazines; D013449:Sulfonamides; D000001:Calcimycin; D013917:Thrombin