He Jinyi, Zhao Yifan, Zhu Tingting, Xue Peng, Zheng Weiwei, Yao Ye, Qu Weidong, Jia Xiaodong, Lu Rongzhu, He Miao, Zhang Yubin
School of Public Health and Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China.
Shanghai Chemical Industry Park Medical Center, Shanghai 201507, China.
Toxics. 2021 Oct 7;9(10):252. doi: 10.3390/toxics9100252.
Inorganic mercury (Hg) is a highly toxic heavy metal. The aim of this study was to investigate the impact of Hg on the development of erythrocytes and megakaryocytes. B10.S mice (H-2) and DBA/2 mice (H-2) were administrated with 10 μM HgCl or 50 μM HgCl via drinking water for four weeks, and erythro-megakaryopoiesis was evaluated thereafter. The administration of 50 μM HgCl increased the number of erythrocytes and platelets in B10.S mice, which was not due to a reduced clearance for mature erythrocytes. The administration of 50 μM HgCl, but not 10 μM HgCl, increased the number of progenitors for erythrocytes and megakaryocytes in the bone marrow (BM) of B10.S mice, including erythroid-megakaryocyte progenitors (EMPs), burst-forming unit-erythroid progenitors (BFU-Es), colony-forming unit-erythroid progenitors (CFU-Es), and megakaryocyte progenitors (MkPs). Moreover, 50 μM HgCl caused EMPs to be more proliferative and possess an increased potential for differentiation into committed progenies in B10.S mice. Mechanistically, 50 μM HgCl increased the expression of the erythropoietin receptor (EPOR) in EMPs, thus enhancing the Jak2/STAT5 signaling pathway to promote erythro-megakaryopoiesis in B10.S mice. Conversely, 50 μM HgCl did not impact erythro-megakaryopoiesis in DBA/2 mice. This study may extend our current understanding for hematopoietic toxicology of Hg.
无机汞(Hg)是一种剧毒重金属。本研究旨在探讨汞对红细胞和巨核细胞发育的影响。通过饮用水给B10.S小鼠(H-2)和DBA/2小鼠(H-2)分别施用10μM HgCl或50μM HgCl,持续四周,之后评估红细胞-巨核细胞生成情况。施用50μM HgCl可增加B10.S小鼠的红细胞和血小板数量,这并非由于成熟红细胞清除率降低所致。施用50μM HgCl而非10μM HgCl可增加B10.S小鼠骨髓中红细胞和巨核细胞祖细胞的数量,包括红系-巨核细胞祖细胞(EMP)、爆式红系集落形成祖细胞(BFU-E)、红系集落形成祖细胞(CFU-E)和巨核细胞祖细胞(MkP)。此外,50μM HgCl使B10.S小鼠中的EMP更具增殖性且分化为定向祖细胞的潜力增加。机制上,50μM HgCl增加了EMP中促红细胞生成素受体(EPOR)的表达,从而增强Jak2/STAT5信号通路以促进B10.S小鼠的红细胞-巨核细胞生成。相反,50μM HgCl对DBA/2小鼠的红细胞-巨核细胞生成没有影响。本研究可能会扩展我们目前对汞造血毒理学的认识。