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通过在气液界面暴露培养的人肺细胞评估空气中颗粒物的急性吸入毒性。

Assessment of the Acute Inhalation Toxicity of Airborne Particles by Exposing Cultivated Human Lung Cells at the Air-Liquid Interface.

作者信息

Tsoutsoulopoulos Amelie, Gohlsch Katrin, Möhle Niklas, Breit Andreas, Hoffmann Sebastian, Krischenowski Olaf, Mückter Harald, Gudermann Thomas, Thiermann Horst, Aufderheide Michaela, Steinritz Dirk

机构信息

Bundeswehr Institute of Pharmacology and Toxicology;

Walther Straub Institute of Pharmacology and Toxicology, University of Munich.

出版信息

J Vis Exp. 2020 Feb 23(156). doi: 10.3791/60572.

Abstract

Here, we present a specially designed modular in vitro exposure system that enables the homogenous exposure of cultivated human lung cells at the ALI to gases, particles or complex atmospheres (e.g., cigarette smoke), thus providing realistic physiological exposure of the apical surface of the human alveolar region to air. In contrast to sequential exposure models with linear aerosol guidance, the modular design of the radial flow system meets all requirements for the continuous generation and transport of the test atmosphere to the cells, a homogenous distribution and deposition of the particles and the continuous removal of the atmosphere. This exposure method is primarily designed for the exposure of cells to airborne particles, but can be adapted to the exposure of liquid aerosols and highly toxic and aggressive gases depending on the aerosol generation method and the material of the exposure modules. Within the framework of a recently completed validation study, this exposure system was proven as a transferable, reproducible and predictive screening method for the qualitative assessment of the acute pulmonary cytotoxicity of airborne particles, thereby potentially reducing or replacing animal experiments that would normally provide this toxicological assessment.

摘要

在此,我们展示了一种专门设计的模块化体外暴露系统,该系统能够使培养的人肺细胞在气液界面(ALI)均匀暴露于气体、颗粒或复杂大气环境(如香烟烟雾)中,从而使人肺泡区域的顶端表面实现对空气的真实生理性暴露。与具有线性气溶胶引导的顺序暴露模型不同,径向流系统的模块化设计满足了将测试大气连续生成并输送至细胞、颗粒均匀分布与沉积以及大气连续去除的所有要求。这种暴露方法主要设计用于细胞对空气中颗粒的暴露,但根据气溶胶生成方法和暴露模块的材料,可适用于液体气溶胶以及剧毒和腐蚀性气体的暴露。在最近完成的一项验证研究框架内,该暴露系统被证明是一种可转移、可重复且具有预测性的筛选方法,用于定性评估空气中颗粒的急性肺细胞毒性,从而有可能减少或替代通常用于提供这种毒理学评估的动物实验。

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