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Thromb Haemost 2021; 121(04): 495-505
DOI: 10.1055/s-0040-1718761
Cellular Haemostasis and Platelets

Immune Thrombocytopenia Plasma-Derived Exosomes Impaired Megakaryocyte and Platelet Production through an Apoptosis Pathway

Wenjing Miao
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
2   Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China
3   Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
,
Baoquan Song
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
2   Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China
3   Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
,
Bingyu Shi
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
2   Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China
3   Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
,
Qi Wan
4   Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, of China
,
Quansheng Lv
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
,
Hanqing Chen
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
,
Mingqing Zhu
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
,
Leisheng Zhang
5   The Postdoctoral Research Station, School of Medicine, Nankai University, Tianjin, China
6   Division of Precision Medicine, Health-Biotech (Tianjin) Stem Cell Research Institute Co., Ltd., Tianjin, China
,
Yue Han
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
2   Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China
3   Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
,
Depei Wu
1   National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
2   Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, China
3   Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
› Author Affiliations Funding This work was supported by the National Natural Science Foundation of China (No. 81700119), China Postdoctoral Science Foundation (2019M661033), the Natural Science Foundation of Tianjin (19JCQNJC12500).
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Abstract

Reduced megakaryocyte (MK) apoptosis and insufficient platelet production play important roles in the pathogenesis of immune thrombocytopenia (ITP). The contribution of plasma-derived exosomes to the decreased platelet count in ITP has not been entirely understood. Here, we found the percentage of apoptotic MKs in patients with ITP was significantly lower than those in healthy volunteers. In the presence of ITP plasma-derived exosomes (ITP-Exo), the apoptosis of MKs was reduced during the process of MK differentiation in vitro, which contributed to the reduced platelet production by Bcl-xL/caspase signaling. Furthermore, in vivo study demonstrated that ITP-Exo administration led to significantly delayed platelet recovery in mice after 3.5 Gy of irradiation. All these findings indicated that ITP-Exo, as a regulator of platelet production, impaired MK apoptosis and platelet production through Bcl-xL/caspase signaling, unveiling new mechanisms for reduced platelet count in ITP.

Keywords

immune thrombocytopenia - exosomes - megakaryocyte - platelets - apoptosis

∗ W.M. and B.S. contributed equally to this study.


Supplementary Material



Publication History

Received: 18 August 2019

Accepted: 15 September 2020

Article published online:
29 October 2020

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