School of Public Health, Qingdao University, 38 Dengzhou Road, Qingdao 266021, China; National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing 100050, China.
National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing 100050, China.
Toxicol In Vitro. 2019 Sep;59:263-274. doi: 10.1016/j.tiv.2019.04.026. Epub 2019 Apr 25.
Oxidative stress is usually considered to be a common mechanism by which particulate matter (PM) exposure induces adverse effects. However, the further biological events such as organelle dysfunction following oxidative stress remain to be explored. In this study, we applied high-content screening (HCS) technique to investigate the toxicological effects of carbon black (CB), diesel exhaust particle (DEP) and PM2.5 on oxidative stress and organelle function in human bronchial epithelial cell (16HBE), human embryo lung fibroblast cell (HELF) and human umbilical vein endothelial cell (HUVEC) which were used to represent distinct regions of the lung, and compared the toxicity impacts of different PMs and the sensitiveness of cell lines. We found three types of PMs induced mitochondrial dysfunction in three cell lines and lysosomal alkalinization in HUVEC while only CB triggered endoplasmic reticulum (ER) stress in 16HBE and HUVEC, and oxidative stress might mediate these processes. Moreover, CB basically exhibited more potent toxicity compared with DEP and PM2.5, which might be attributed to its less oxygen content. Finally, the finding that PMs-induced toxicity impacts exhibited a cell-type dependent manner might provide some information to help to understand the sensitivity of different tissue in the lung.
氧化应激通常被认为是颗粒物(PM)暴露引起不良反应的共同机制。然而,氧化应激后细胞器功能障碍等进一步的生物学事件仍有待探索。在这项研究中,我们应用高内涵筛选(HCS)技术研究了炭黑(CB)、柴油机排气颗粒物(DEP)和 PM2.5 对人支气管上皮细胞(16HBE)、人胚肺成纤维细胞(HELF)和人脐静脉内皮细胞(HUVEC)氧化应激和细胞器功能的毒理学影响,这些细胞分别代表了肺部的不同区域,并比较了不同 PM 的毒性影响和细胞系的敏感性。我们发现三种 PM 均可诱导三种细胞系中的线粒体功能障碍和 HUVEC 中的溶酶体碱化,而只有 CB 可在 16HBE 和 HUVEC 中引发内质网(ER)应激,氧化应激可能介导了这些过程。此外,CB 与 DEP 和 PM2.5 相比表现出更强的毒性,这可能归因于其较低的含氧量。最后,PM 诱导的毒性影响表现出细胞类型依赖性的方式,这可能为了解肺部不同组织的敏感性提供了一些信息。