Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia.
Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia.
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DOI：
10.1182/blood-2010-02-267435
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发表时间：
2010-11
期刊：
影响因子：
20.3
通讯作者：
Lei Yang;Lin Wang;Chunhong Zhao;Xiao‐juan Zhu;Yu Hou;P. Jun;M. Hou
中科院分区：
文献类型：
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作者：
Lei Yang;Lin Wang;Chunhong Zhao;Xiao‐juan Zhu;Yu Hou;P. Jun;M. Hou
最近的体外研究提供了自身抗体诱导的巨核细胞生成抑制的证据，并显示在存在免疫性血小板减少症（ITP）血浆的情况下，巨核细胞的产生和成熟减少。在本研究中，我们将来自健康脐带血单个核细胞的CD34（+）细胞培养在含有血小板生成素、干细胞因子、白细胞介素-3和10% ITP患者或健康受试者血浆的培养基中。测定巨核细胞的数量、质量和凋亡情况。我们观察到大多数ITP血浆增加了巨核细胞的数量，但损害了质量，导致多倍体细胞（N≥4）和血小板释放显著减少。在这些巨核细胞中，我们发现细胞凋亡率较低，肿瘤坏死因子相关凋亡诱导配体（TRAIL）表达较低，Bcl-xL表达较高。此外，与对照组相比，ITP血浆和细胞培养上清液中sTRAIL含量明显降低。我们的研究结果表明，巨核细胞凋亡的减少也有助于体外巨核细胞异常生成和血小板生成的减少。血浆中sTRAIL和巨核细胞中TRAIL和Bcl-xL的异常表达可能在ITP中巨核细胞凋亡受损的发病机制中起作用。
Recent in vitro studies provide evidence for autoantibody-induced suppression of megakaryocytopoiesis and show a reduction in megakaryocyte production and maturation in the presence of immune thrombocytopenia (ITP) plasma. Here, we present CD34(+) cells from healthy umbilical cord blood mononuclear cells cultured in medium containing thrombopoietin, stem cell factor, interleukin-3, and 10% plasma from either ITP patients or healthy subjects. The quantity, quality, and apoptosis of megakaryocytes were measured. We observed that most ITP plasma boosted megakaryocyte quantity but impaired quality, resulting in significantly less polyploidy cells (N ≥ 4) and platelet release. In these megakaryocytes, we found a lower percentage of cell apoptosis, a lower expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and a higher expression of Bcl-xL. Furthermore, there was a decrease of sTRAIL in ITP plasma and in cell culture supernatants of this group compared with the control group. Our findings suggest that decreased apoptosis of megakaryocytes also contributes to in vitro dysmegakaryocytopoiesis and reduced platelet production. The abnormal expression of sTRAIL in plasma and TRAIL and Bcl-xL in megakaryocytes may play a role in the pathogenesis of impaired megakaryocyte apoptosis in ITP.