Bifunctional effect of the inflammatory cytokine tumor necrosis factor α on megakaryopoiesis and platelet production
Bifunctional effect of the inflammatory cytokine tumor necrosis factor α on megakaryopoiesis and platelet production
复制标题
炎症细胞因子肿瘤坏死因子α对巨核细胞生成和血小板产生的双功能作用
DOI：
10.1111/jth.15891
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发表时间：
2022-10-13
影响因子：
10.4
通讯作者：
Wu, De-Pei
中科院分区：
文献类型：
--
作者：
Chu, Tiantian;Hu, Shuhong;Wu, De-Pei
背景和目的：血小板受到许多因素的影响，如感染性或无菌性炎症，不同的炎症状态可能导致血小板减少或血小板增多。肿瘤坏死因子α (TNF α)是一种重要的炎性细胞因子，已被证明可以影响造血干细胞的活性。然而，它在巨核细胞（MK）发育和血小板产生中的作用仍然很大程度上未知。本研究旨在探讨TNF α对MK和血小板生成的影响。方法和结果：人CD34（+）细胞的离体研究表明，TNF α对MK谱系的承诺有差异调节。具体来说，0.5 ng/ml的低浓度TNF α促进MK成熟、血小板形成和血小板产生，而10 ng/ml或更高浓度的TNF α对MK和血小板产生有明显的抑制作用。TNF α对mk的明显作用主要依赖于TNF α受体1。TNF α差异调节MAPK-ERK1/2信号通路和细胞骨架蛋白cofilin和MLC2。Balb/c小鼠的体内研究表明，低剂量或高剂量TNF α给药对骨髓移植后短期血小板恢复的影响存在差异。结论：我们的研究揭示了TNF α在巨核生成和血小板生成中的独特作用，并可能为血小板疾病的治疗提供新的见解。
Background and Objectives: Platelets are affected by many factors, such as infectious or aseptic inflammation, and different inflammatory states may induce either thrombocytopenia or thrombocytosis. Tumor necrosis factor alpha (TNF alpha) is an important inflammatory cytokine that has been shown to affect the activity of hematopoietic stem cells. However, its role in megakaryocyte (MK) development and platelet production remains largely unknown. This study aimed to investigate the effects of TNF alpha on MK and platelet generation.Methods and Results: The ex vivo study with human CD34(+) cells demonstrated that TNF alpha differentially modulated commitment toward the MK lineage. Specifically, a low concentration of 0.5 ng/ml TNF alpha promoted MK maturation, proplatelet formation, and platelet production, whereas a high concentration of 10 ng/ml or more TNF alpha exhibited a substantial inhibitory effect on MK and platelet production. The distinct effect of TNF alpha on MKs was mainly dependent on TNF alpha receptor 1. TNF alpha differentially regulated the MAPK-ERK1/2 signaling pathway and the cytoskeletal proteins cofilin and MLC2. The in vivo study with Balb/c mice indicated that low-dose or high-dose TNF alpha administration differentially affected short-term platelet recovery after bone marrow transplantation.Conclusions: Our study revealed distinct roles for TNF alpha in megakaryopoiesis and thrombopoiesis and may provide new insights regarding the treatment for platelet disorders.