Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles.
Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles.
复制标题
将人支气管粘膜模型与Xposeali®相结合，以暴露空气污染纳米颗粒。
DOI：
10.1371/journal.pone.0170428
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Palmberg L
中科院分区：
文献类型：
--
作者：
Ji J;Hedelin A;Malmlöf M;Kessler V;Seisenbaeva G;Gerde P;Palmberg L
在工作场所环境中以及在与环境空气中的颗粒的日常接触中，通过吸入暴露于制剂是非常令人关注的。可靠的人体气道暴露系统将很可能取代动物实验在未来的吸入剂的毒性评估研究。在这项研究中，我们成功地建立了一个组合的曝光系统（XposeALI）与3D模型模拟健康和慢性支气管炎样粘膜通过共培养人原代支气管上皮细胞（PBEC）和成纤维细胞在气液界面（ALI）。通过光镜、共聚焦显微镜、扫描电镜、透射电镜、跨上皮电阻（TEER）测定和RT-PCR等方法观察PBEC在ALI培养条件下的分化情况。两种模型都暴露于尺寸为6-10 nm的钯（Pd）纳米颗粒，类似于现代汽车催化剂释放的那些，使用PreciseInhale®暴露系统的XposeALI模块以三种不同浓度暴露。将3D模型暴露于Pd纳米颗粒诱导IL-8分泌增加，但慢性支气管炎样模型释放的IL-8显著多于正常模型。基础培养基（BM）和根尖灌洗液（AM）中IL-8的水平在相同范围内，但AM中MMP-9的分泌显著高于BM。这种相关的人类支气管粘膜模型和复杂的暴露系统的组合可以模拟体内条件，并在研究职业环境中暴露于气溶胶、空气污染物或颗粒的人类的不良影响时，作为一种有用的替代动物试验工具。
Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents. In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6–10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system. Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM. This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.