Lead transiently promotes granulocyte-macrophage progenitor differentiation and subsequently suppresses common myeloid progenitor differentiation.

Lead (Pb) is a toxic heavy metal affecting human health; it is known to be harmful to various organs or systems, yet the mechanisms by which Pb influences immune cell development remain to be defined. In this study, we show that Pb exposure (1250 ppm via drinking water) selectively impacted the development of myeloid cells (myelopoiesis). After Pb treatment of adult C57BL/6 mice, the numbers of granulocyte-macrophage progenitors (GMP) were consistently reduced, while the numbers of myeloid cells were increased at week (wk) 1 and decreased at wk8 after initiating the Pb exposure. Functional assays indicate that Pb accelerated GMP differentiation in a reactive oxygen species (ROS)-dependent manner after treatment for 1 wk and inhibited common myeloid progenitor (CMP) differentiation by upregulating interferon regulatory factor 8 (IRF8) expression after treatment for 8 wks. Consistent with the distinct Pb influences on myeloid cells observed at wk1 and wk8, Pb caused an inflammatory environment in vivo at wk8, but not at wk1. Furthermore, like the observations in mice during the Pb exposure, bloods from humans occupationally exposed to Pb had their numbers of monocytes, neutrophils and GMP negatively associated with the Pb concentration, while IRF8 expression in CMP, but not GMP, was positively correlated with the Pb concentration. These data suggest an occupationally relevant level of Pb exposure preferentially influences myelopoiesis involving ROS and IRF8, which may contribute to the current understanding of the hematopoietic toxicology of Pb. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Citation

Qian Li, Peng Zhang, Xinchun Yu, Yifan Zhao, Qiang Li, Yandong Zhang, Zhengli Yang, Yunli Xie, Peng Xue, Shuhui Sun, Xiaodong Jia, Zhijun Zhou, Miao He, Yubin Zhang. Lead transiently promotes granulocyte-macrophage progenitor differentiation and subsequently suppresses common myeloid progenitor differentiation. Toxicological sciences : an official journal of the Society of Toxicology. 2017 Aug 30

PMID: 28973681

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