Inhibition of GPIb-α-mediated apoptosis signaling enables cold storage of platelets
Cold storage of platelets has been suggested as an alternative approach to reduce the risk of bacterial contamination and to improve the cell quality as well as functionality compared to room temperature storage. However, cold-stored platelets (CSP) are rapidly cleared from the circulation. Among several possible mechanisms, apoptosis has been recently proposed to be responsible for the short half-life of refrigerated platelets. In the present study, we investigated the impact of apoptosis inhibition on the hemostatic functions and survival of CSP. We found that blocking the transduction of the apoptotic signal induced by glycoprotein Ib (GPIb)-α clustering or the activation of caspase 9 does not impair CSP functionality. In fact, the inhibition of GPIb-α clustering mediated-apoptotic signal by a RhoA inhibitor better conserved δ granule release, platelet aggregation, adhesion and the ability to form stable clots, compared to untreated CSP. In contrast, upregulation of the protein kinase A caused a drastic impairment of platelet functions and whole blood clot stability. More importantly, we observed a significant improvement of the half-life of CSP upon inhibition of the intracellular signal induced by GPIb-α clustering. In conclusion, our study provides novel insights on the in vitro hemostatic functions and half-life of CSP upon inhibition of the intracellular cold-induced apoptotic pathway. Our data suggest that the combination of cold storage and apoptosis inhibition might be a promising strategy to prolong the storage time without impairing hemostatic functions or survival of refrigerated platelets.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
|---|---|
| Enthalten in: |
Haematologica - 108(2023), 11 vom: 01. Nov., Seite 2959-2971 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Marini, Irene [VerfasserIn] |
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| Links: |
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| Themen: |
Hemostatics |
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| Anmerkungen: |
Date Completed 03.11.2023 Date Revised 07.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3324/haematol.2022.282572 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358469120 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Cold storage of platelets has been suggested as an alternative approach to reduce the risk of bacterial contamination and to improve the cell quality as well as functionality compared to room temperature storage. However, cold-stored platelets (CSP) are rapidly cleared from the circulation. Among several possible mechanisms, apoptosis has been recently proposed to be responsible for the short half-life of refrigerated platelets. In the present study, we investigated the impact of apoptosis inhibition on the hemostatic functions and survival of CSP. We found that blocking the transduction of the apoptotic signal induced by glycoprotein Ib (GPIb)-α clustering or the activation of caspase 9 does not impair CSP functionality. In fact, the inhibition of GPIb-α clustering mediated-apoptotic signal by a RhoA inhibitor better conserved δ granule release, platelet aggregation, adhesion and the ability to form stable clots, compared to untreated CSP. In contrast, upregulation of the protein kinase A caused a drastic impairment of platelet functions and whole blood clot stability. More importantly, we observed a significant improvement of the half-life of CSP upon inhibition of the intracellular signal induced by GPIb-α clustering. In conclusion, our study provides novel insights on the in vitro hemostatic functions and half-life of CSP upon inhibition of the intracellular cold-induced apoptotic pathway. Our data suggest that the combination of cold storage and apoptosis inhibition might be a promising strategy to prolong the storage time without impairing hemostatic functions or survival of refrigerated platelets | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Platelet Glycoprotein GPIb-IX Complex |2 NLM | |
| 650 | 7 | |a Hemostatics |2 NLM | |
| 700 | 1 | |a Pelzl, Lisann |e verfasserin |4 aut | |
| 700 | 1 | |a Tamamushi, Yoko |e verfasserin |4 aut | |
| 700 | 1 | |a Maettler, Chiara-Tanita |e verfasserin |4 aut | |
| 700 | 1 | |a Witzemann, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Althaus, Karina |e verfasserin |4 aut | |
| 700 | 1 | |a Nowak-Harnau, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Seifried, Erhard |e verfasserin |4 aut | |
| 700 | 1 | |a Bakchoul, Tamam |e verfasserin |4 aut | |
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