Veranth John M, Kaser Erin G, Veranth Martha M, Koch Michael, Yost Garold S
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.
Part Fibre Toxicol. 2007 Feb 27;4:2. doi: 10.1186/1743-8977-4-2.
The induction of cytokines by airway cells in vitro has been widely used to assess the effects of ambient and occupational particles. This study measured cytotoxicity and the release of the proinflammatory cytokines IL-6 and IL-8 by human bronchial epithelial cells treated with manufactured nano- and micron-sized particles of Al2O3, CeO2, Fe2O3, NiO, SiO2, and TiO2, with soil-derived particles from fugitive dust sources, and with the positive controls LPS, TNF-alpha, and VOSO4.
The nano-sized particles were not consistently more potent than an equal mass of micron-sized particles of the same nominal composition for the induction of IL-6 and IL-8 secretion in the in vitro models used in this study. The manufactured pure oxides were much less potent than natural PM2.5 particles derived from soil dust, and the cells were highly responsive to the positive controls. The nano-sized particles in the media caused artifacts in the measurement of IL-6 by ELISA due to adsorption of the cytokine on the high-surface-area particles. The potency for inducing IL-6 secretion by BEAS-2B cells did not correlate with the generation of reactive oxygen species in cell-free media.
Direct comparisons of manufactured metal oxide nanoparticles and previously studied types of particles and surrogate proinflammatory agonists showed that the metal oxide particles have low potency to induce IL-6 secretion in BEAS-2B cells. Particle artifacts from non-biological effects need to be considered in experiments of this type, and the limitations inherent in cell culture studies must be considered when interpreting in vitro results. This study suggests that manufactured metal oxide nanoparticles are not highly toxic to lung cells compared to environmental particles.
气道细胞在体外诱导细胞因子已被广泛用于评估环境和职业颗粒物的影响。本研究测量了用人工制造的纳米级和微米级的氧化铝、二氧化铈、氧化铁、氧化镍、二氧化硅和二氧化钛颗粒、来自扬尘源的土壤衍生颗粒以及阳性对照脂多糖、肿瘤坏死因子-α和硫酸氧钒处理的人支气管上皮细胞的细胞毒性以及促炎细胞因子白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的释放。
在本研究使用的体外模型中,对于诱导IL-6和IL-8分泌而言,纳米级颗粒并不总是比相同标称组成的等质量微米级颗粒更有效。人工制造的纯氧化物的效力远低于源自土壤灰尘的天然细颗粒物(PM2.5),并且细胞对阳性对照高度敏感。由于细胞因子吸附在高表面积颗粒上,培养基中的纳米级颗粒在通过酶联免疫吸附测定法(ELISA)测量IL-6时会产生假象。BEAS-2B细胞诱导IL-6分泌的效力与无细胞培养基中活性氧的产生无关。
对人工制造的金属氧化物纳米颗粒与先前研究的颗粒类型和替代促炎激动剂的直接比较表明,金属氧化物颗粒在BEAS-2B细胞中诱导IL-6分泌的效力较低。在这类实验中需要考虑非生物学效应产生的颗粒假象,并且在解释体外结果时必须考虑细胞培养研究固有的局限性。本研究表明,与环境颗粒相比,人工制造的金属氧化物纳米颗粒对肺细胞的毒性不高。