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氧化铟纳米颗粒诱导支气管上皮细胞和巨噬细胞间的肺细胞间毒性。

Indium oxide nanoparticles induce lung intercellular toxicity between bronchial epithelial cells and macrophages.

机构信息

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.

Shool of the Environment, Nanjing University, Nanjing, China.

出版信息

J Appl Toxicol. 2020 Dec;40(12):1636-1646. doi: 10.1002/jat.4023. Epub 2020 Jul 1.

DOI:10.1002/jat.4023
PMID:32608070
Abstract

Concerns have been raised over the safety and health of industrial workers exposed to indium oxide nanoparticles (IO-NPs) when working. IO-NPs were previously shown in vitro and in vivo to be cytotoxic, but the mechanism of pathogenesis was unclear. In this study, the effects of IO-NPs on lung cells associated with respiratory and immune barriers and the toxic effects of intercellular cascades were studied. Here IO-NPs had acute toxicity to Wistar rats over a time course (5 days post-intratracheal instillation). Following treatment epithelial cells (16HBE) or macrophages (RAW264.7) with IO-NPs or IO fine particles (IO-FPs), the damage of 16HBE cells caused by IO-NPs was serious, mainly in the mitochondrial and rough endoplasmic reticulum. The lactate dehydrogenase level also showed that cytotoxicity in vitro was more serious for IO-NPs compared with IO-FPs. The level of In (examined by inductively coupled plasma mass spectrometry) in 16HBE cells was 10 times higher than that in RAW cells. In , releasing from IO-NPs absorbed by 16HBE cells, could not only significantly inhibit the phagocytosis and migration of macrophages (P < .0001), but also stimulate RAW cells to secrete high levels of inflammatory cytokines. IO-NPs can directly damage pulmonary epithelial cells. The In released by epithelial cells affect the phagocytosis and migration of macrophages, which may be a new point for the decrease in the clearance of alveolar surfactants and the development of IO-related pulmonary alveolar proteinosis.

摘要

人们对从事接触氧化铟纳米粒子(IO-NPs)工作的工业工人的安全和健康表示担忧。先前的研究表明,IO-NPs 在体外和体内均具有细胞毒性,但发病机制尚不清楚。在这项研究中,研究了 IO-NPs 对与呼吸和免疫屏障相关的肺细胞的影响,以及细胞间级联的毒性作用。在此,IO-NPs 在一段时间内(气管内滴注后 5 天)对 Wistar 大鼠具有急性毒性。用 IO-NPs 或 IO 细颗粒(IO-FPs)处理上皮细胞(16HBE)或巨噬细胞(RAW264.7)后,IO-NPs 对 16HBE 细胞的损伤严重,主要在线粒体和粗面内质网。乳酸脱氢酶水平也表明,与 IO-FPs 相比,IO-NPs 的体外细胞毒性更严重。通过电感耦合等离子体质谱法(ICP-MS)检测,16HBE 细胞中的 In(铟)水平是 RAW 细胞的 10 倍。在,从被 16HBE 细胞吸收的 IO-NPs 中释放出来的,不仅可以显著抑制巨噬细胞的吞噬和迁移(P <.0001),还可以刺激 RAW 细胞分泌高水平的炎症细胞因子。IO-NPs 可直接损伤肺上皮细胞。上皮细胞释放的 In 影响巨噬细胞的吞噬和迁移,这可能是肺泡表面活性剂清除减少和 IO 相关的肺泡蛋白沉积症发展的一个新点。

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