Increasing use of engineered nanomaterials (ENMs) means increased human exposures. Potential adverse effects include those on the immune system, ranging from direct toxicity to impairment of defenses against environmental pathogens and toxins. Effects on lung macrophages may be especially prominent, because they serve to clear foreign materials like ENMs and bacterial pathogens. We investigated the effects of 4 hour exposures over a range of concentrations, of a panel of industry-relevant ENMs, including SiO2, Fe2O3, ZnO, CeO2, TiO2, and an Ag/SiO2 composite, on human THP-1 macrophages. Effects on phagocytosis of latex beads, and phagocytosis and killing of Francisella tularensis (FT), as well as viability, oxidative stress and mitochondrial integrity, were measured by automated scanning confocal microscopy and image analysis. Results revealed some notable patterns: 1) Phagocytosis of unopsonized beads was increased, whereas that of opsonized beads was decreased, by all ENMs, with the exception of ZnO, which reduced both opsonized and unopsonized uptake; 2) Uptake of opsonized and unopsonized FT was either impaired or unaffected by all ENMs, with the exception of CeO2, which increased phagocytosis of unopsonized FT; 3) Macrophage killing of FT tended to improve with all ENMs; and 4) Viability was unaffected immediately following exposures with all ENMs tested, but was significantly decreased 24 hours after exposures to Ag/SiO2 and ZnO ENMs. The results reveal a complex landscape of ENM effects on macrophage host defenses, including both enhanced and reduced capacities, and underscore the importance of robust hazard assessment, including immunotoxicity assessment, of ENMs.

中文翻译：

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工程纳米材料暴露对巨噬细胞先天免疫功能的影响

越来越多地使用工程纳米材料 (ENM) 意味着人类暴露的增加。潜在的不利影响包括对免疫系统的影响，从直接毒性到对环境病原体和毒素的防御能力受损。对肺巨噬细胞的影响可能特别突出，因为它们有助于清除外来物质，如 ENM 和细菌病原体。我们研究了一系列工业相关 ENM（包括 SiO2、Fe2O3、ZnO、CeO2、TiO2 和 Ag/SiO2 复合物）在一系列浓度范围内暴露 4 小时对人类 THP-1 巨噬细胞的影响。通过自动扫描共聚焦显微镜和图像分析测量对乳胶珠吞噬作用、土拉弗朗西斯菌 (FT) 吞噬作用和杀死作用以及活力、氧化应激和线粒体完整性的影响。结果揭示了一些显着的模式：1) 所有 ENMs 都增加了未经调理的珠子的吞噬作用，而调理的珠子的吞噬作用却降低了，除了 ZnO，它减少了调理和未经调理的吸收；2) 除 CeO2 外，所有 ENM 均损害或不影响调理和未调理 FT 的摄取，CeO2 增加了未调理 FT 的吞噬作用；3) FT 的巨噬细胞杀伤趋向于随着所有 ENM 的出现而改善；和 4) 在暴露于所有测试的 ENM 后，活力不立即受到影响，但在暴露于 Ag/SiO2 和 ZnO ENM 后 24 小时显着降低。结果揭示了 ENM 对巨噬细胞宿主防御的复杂影响，包括增强和降低的能力，并强调了稳健的危害评估的重要性，包括免疫毒性评估，