Shaoheng Chen , Jia Han , Huimin Deng , Yuanshan Lu , Zhicheng Wang , Qi Zhang , Rong Xia
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引用次数: 0
Abstract
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.
期刊介绍:
Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.