Use of EpiAlveolar Lung Model to Predict Fibrotic Potential of Multiwalled Carbon Nanotubes
Use of EpiAlveolar Lung Model to Predict Fibrotic Potential of Multiwalled Carbon Nanotubes
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DOI：
10.1021/acsnano.9b06860
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发表时间：
2020-04-28
期刊：
影响因子：
17.1
通讯作者：
Rothen-Rutishauser, Barbara
中科院分区：
文献类型：
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作者：
Barosova, Hana;Maione, Anna G.;Rothen-Rutishauser, Barbara
纳米材料的生产和商业使用的扩大增加了人类在这些材料的生命周期（生产、使用和处置）中的潜在接触。吸入是接触纳米材料的主要途径;因此，评估其潜在的呼吸危害至关重要。在此，我们开发了一个三维肺泡模型（EpiAlveolar），包括人原代肺泡上皮细胞，成纤维细胞和内皮细胞，有或没有巨噬细胞预测长期响应气溶胶。在对模型进行全面表征后，基于肺纤维化不良结局途径概念，在重复亚慢性暴露（长达21天）两种类型的多壁碳纳米管（MWCNT）和二氧化硅石英颗粒后评估促炎和促纤维化反应。我们模拟职业暴露剂量的多壁碳纳米管（1-30 μ g/cm（2））使用空气-液体界面暴露装置（VITROCELL云）与重复暴露超过3周。导致肺纤维化的特定关键事件，如屏障完整性和促炎性和促纤维化标志物的释放，显示了模型的响应性。总的来说，Nanocyl诱导的反应不如Mitsui-7明显，并且含有人单核细胞衍生巨噬细胞（MDM）的培养物在比不含MDM的培养物更晚的时间点显示出促炎症反应。总之，我们提出了一个强大的肺泡模型来预测暴露于多壁碳纳米管后的炎症和纤维化反应。
Expansion in production and commercial use of nanomaterials increases the potential human exposure during the lifecycle of these materials (production, use, and disposal). Inhalation is a primary route of exposure to nanomaterials; therefore it is critical to assess their potential respiratory hazard. Herein, we developed a three-dimensional alveolar model (EpiAlveolar) consisting of human primary alveolar epithelial cells, fibroblasts, and endothelial cells, with or without macrophages for predicting long-term responses to aerosols. Following thorough characterization of the model, proinflammatory and profibrotic responses based on the adverse outcome pathway concept for lung fibrosis were assessed upon repeated subchronic exposures (up to 21 days) to two types of multiwalled carbon nanotubes (MWCNTs) and silica quartz particles. We simulate occupational exposure doses for the MWCNTs (1-30 mu g/cm(2)) using an air-liquid interface exposure device (VITROCELL Cloud) with repeated exposures over 3 weeks. Specific key events leading to lung fibrosis, such as barrier integrity and release of proinflammatory and profibrotic markers, show the responsiveness of the model. Nanocyl induced, in general, a less pronounced reaction than Mitsui-7, and the cultures with human monocyte-derived macrophages (MDMs) showed the proinflammatory response at later time points than those without MDMs. In conclusion, we present a robust alveolar model to predict inflammatory and fibrotic responses upon exposure to MWCNTs.