Nanoparticle induced barrier function assessment at liquid–liquid and air–liquid interface in novel human lung epithelia cell lines,Toxicology Research

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Nanoparticle induced barrier function assessment at liquid–liquid and air–liquid interface in novel human lung epithelia cell lines
Toxicology Research ( IF 2.2 ) Pub Date : 2019-11-19 , DOI: 10.1039/c9tx00179d
Lars Leibrock ₁ , Sandra Wagener ₁ , Ajay Vikram Singh ₁ , Peter Laux ₁ , Andreas Luch ₁

Affiliation

Inhalation is the most relevant entry point for nanoparticles (NPs) into the human body. To date, toxicity testing of nanomaterials in respect to oral, dermal and inhalative application is mainly based on animal experiments. The development of alternative test methods is the subject of current research. In vitro models can help to investigate mechanistic aspects, as e.g. cellular uptake or genotoxicity and might help to reduce in vivo testing. Lung cell lines are proper in vitro tools to assess NP toxicity. In respect to this, various cell models have been developed during the recent years, but often lack in a proper intact barrier function. However, besides other important in vivo criteria which are still missing like e.g. circulation, this is one basic prerequisite to come closer to the in vivo situation in certain mechanistic aspects such as particle translocation which is an important task for risk assessment of nanomaterials. Novel developed in vitro models may help to investigate the translocation of nanomaterials from the lung. We investigated the barrier function of the recently developed human lung cell lines CI-hAELVi and CI-huAEC. The cells were further exposed to CeO₂ NPs and ZnO NPs, and their suitability as in vitro models for toxicological investigations was proven. The obtained data were compared with data generated with the A549 cell line. Measurement of transepithelial resistance and immunohistochemical examination of tight junctions confirmed the formation of a functional barrier for both cell lines for submerged and air–liquid cultivation. For particle exposure, hAELVi and huAEC cells showed comparable results to A549 cells without losing the barrier function. CeO₂ NP exposure revealed no toxicity for all cell lines. In contrast, ZnO NPs was toxic for all cell lines at a concentration between 10–50 μg ml⁻¹. Due to the comparable results to A549 cells CI-hAELVi and CI-huAEC offer new opportunities to investigate nanoparticle cell interactions more realistic than recent 2D cell models.

中文翻译：

新型人肺上皮细胞系液-液和气-液界面纳米颗粒诱导的屏障功能评估

吸入是纳米颗粒 (NP) 进入人体最相关的入口点。迄今为止，纳米材料的口服、皮肤和吸入毒性测试主要基于动物实验。替代测试方法的开发是当前研究的主题。体外模型可以帮助研究机制方面，例如细胞摄取或遗传毒性，并且可能有助于减少体内测试。肺细胞系是评估 NP 毒性的合适体外工具。就此而言，近年来已经开发了各种细胞模型，但通常缺乏适当的完整屏障功能。然而，除了仍然缺少其他重要的体内标准（例如循环）之外，这是在某些机械方面（例如粒子易位）更接近体内情况的一个基本先决条件，这是纳米材料风险评估的一项重要任务。新开发的体外模型可能有助于研究纳米材料从肺部的易位。我们研究了最近开发的人肺细胞系 CI-hAELVi 和 CI-huAEC 的屏障功能。将细胞进一步暴露于CeO ₂ NPs和ZnO NPs，并证明它们作为毒理学研究的体外模型的适用性。将获得的数据与 A549 细胞系生成的数据进行比较。跨上皮电阻的测量和紧密连接的免疫组织化学检查证实了用于浸没和气液培养的两种细胞系的功能屏障的形成。对于颗粒暴露，hAELVi和huAEC细胞显示出与A549细胞相当的结果，且不丧失屏障功能。 CeO ₂ NP 暴露对所有细胞系均无毒性。相反，浓度在10-50 μg ml ^-1之间的ZnO NPs 对所有细胞系都是有毒的。由于与 A549 细胞的结果相似，CI-hAELVi 和 CI-huAEC 为研究纳米粒子细胞相互作用提供了新的机会，比最近的 2D 细胞模型更真实。

更新日期：2019-11-19

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