DeLoid Glen, Casella Beatriz, Pirela Sandra, Filoramo Rose, Pyrgiotakis Georgios, Demokritou Philip, Kobzik Lester
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard School of Public Health, Boston, MA, United States of America.
Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
NanoImpact. 2016 Apr;2:70-81. doi: 10.1016/j.impact.2016.07.001. Epub 2016 Jul 25.
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 SiO, FeO, ZnO, CeO, TiO, and an Ag/SiO2 composite, on human THP-1 macrophages. Effects on phagocytosis of latex beads, and phagocytosis and killing of (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 CeO, 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/SiO 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.
工程纳米材料(ENM)使用的增加意味着人类接触的增加。潜在的不利影响包括对免疫系统的影响,从直接毒性到对抵御环境病原体和毒素的防御能力的损害。对肺巨噬细胞的影响可能尤为突出,因为它们有助于清除诸如ENM和细菌病原体等外来物质。我们研究了一系列与行业相关的ENM,包括SiO、FeO、ZnO、CeO、TiO以及一种Ag/SiO2复合材料,在一系列浓度下4小时暴露对人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了对乳胶珠吞噬作用、对(FT)的吞噬和杀伤作用,以及活力、氧化应激和线粒体完整性。结果揭示了一些显著模式:1)除ZnO降低调理和未调理摄取外,所有ENM均增加未调理珠的吞噬作用,而降低调理珠的吞噬作用;2)除CeO增加未调理FT的吞噬作用外,所有ENM对调理和未调理FT的摄取均受损或未受影响;3)所有ENM对FT的巨噬细胞杀伤作用均趋于改善;4)在测试的所有ENM暴露后,活力立即未受影响,但在暴露于Ag/SiO和ZnO ENM 24小时后显著降低。结果揭示了ENM对巨噬细胞宿主防御影响的复杂情况,包括增强和降低的能力,并强调了对ENM进行强有力的危害评估(包括免疫毒性评估)的重要性。