Platelet PD-L1 inhibits storage-induced apoptosis by sustaining activation of the AKT signalling pathway

Platelet apoptosis is irreversible under current storage conditions in blood banks. Studies have shown that programmed cell death ligand 1 (PD-L1) in tumour cells is required for neoplastic progression, tumour recurrence and metastasis by regulating apoptosis. However, whether PD-L1 is involved in s...

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Veröffentlicht in:Thrombosis research 2024-08, Vol.240, p.109056, Article 109056
Hauptverfasser: Chen, Shaoheng, Han, Jia, Deng, Huimin, Lu, Yuanshan, Wang, Zhicheng, Zhang, Qi, Xia, Rong
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Sprache:eng
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Zusammenfassung:Platelet apoptosis is irreversible under current storage conditions in blood banks. Studies have shown that programmed cell death ligand 1 (PD-L1) in tumour cells is required for neoplastic progression, tumour recurrence and metastasis by regulating apoptosis. However, whether PD-L1 is involved in storage-induced apoptosis in platelets remains poorly understood. In this study, we explored whether PD-L1 on platelets participated in the regulation of storage-induced apoptosis under blood bank conditions, as well as the underlying mechanism. Several apoptotic events in platelets from humans and PD-L1-knockout mice during storage under blood bank conditions were measured. The mechanism by which storage-induced apoptosis was regulated by platelet-intrinsic PD-L1 signalling was further investigated. Our results showed that PD-L1 in platelets progressively decreased. There was a strong negative correlation between platelet PD-L1 expression and the phosphatidylserine (PS) externalization rate and cleaved caspase-3 level and a positive correlation with anti-apoptosis protein Bcl-xl. Ex vivo, PD-L1−/− platelets stored at 22 °C showed rapid apoptosis via an intrinsic mitochondria-dependent pathway over time. Likewise, inhibiting PD-L1 signalling with BMS-1166 accelerated apoptosis by intrinsic mitochondria-dependent pathway. Coimmunoprecipitation analysis revealed that PD-L1 could bind AKT in platelets, and the binding capacity of both showed a progressive decrease with time. Finally, the decrease in PD-L1 expression levels during storage could be attributed to a complex process of progressive secretion. Therefore, platelet PD-L1 inhibits storage-induced apoptosis by sustaining activation of the AKT signalling pathway, which is expected to become a target for alleviating platelet storage lesions (PSLs) under current blood bank conditions. [Display omitted] •A decreased abundance of PD-L1 in stored platelet, negatively correlated with the level of storage-induced apoptosis.•PD-L1 knockout or blockade promoted an intrinsic mitochondria-dependent apoptosis through AKT signalling pathway•A progressive secretion from platelets during storage attributed to the decreased expression of PD-L1.
ISSN:0049-3848
1879-2472
1879-2472
DOI:10.1016/j.thromres.2024.109056