Studies on health effects of engineered nanomaterials (ENM) in the lung has provided information on ENM toxicity and translocation across airway and alveolar epithelial barriers. Various inhaled ENM (e.g., gold and iridium nanoparticles) have been reported to partially cross the air-blood barrier in the lung, enter the vasculature and distribute in several end organs including heart, liver, spleen and kidney. Using an in vitro primary rat alveolar epithelial cell (AEC) monolayer model, we reported transport rates of relatively non-toxic polystyrene nanoparticles (PNP), which appear to be taken up via non-endocytic processes into AEC. PNP internalized into cytoplasm then trigger autophagy, followed by delivery of PNP from autophagosomes into lysosomes, from where PNP are exocytosed. We utilized the data from these experiments to perform biokinetic modeling that incorporates the processes associated with internalization and intracellular distribution of PNP, autophagy, lysosomal exocytosis of PNP, and several putative mechanisms of action that extend our previous understanding of AEC processing of PNP. Results suggest that entry of PNP into AEC, subsequent activation of autophagy by cytosolic PNP, accumulation of PNP in lysosomes, and lysosomal exocytosis are interwoven by proposed regulatory mechanisms.

中文翻译：

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纳米颗粒与肺泡上皮细胞相互作用的生物动力学建模：摄取、细胞内加工和出口

对肺中工程纳米材料 (ENM) 的健康影响的研究提供了有关 ENM 毒性和跨气道和肺泡上皮屏障易位的信息。据报道，各种吸入的 ENM（例如，金和铱纳米粒子）会部分穿过肺中的气血屏障，进入脉管系统并分布在几个终末器官中，包括心脏、肝脏、脾脏和肾脏。使用体外原代大鼠肺泡上皮细胞 (AEC) 单层模型，我们报告了相对无毒的聚苯乙烯纳米粒子 (PNP) 的转运率，它们似乎通过非内吞过程进入 AEC。PNP 内化到细胞质中，然后触发自噬，然后将 PNP 从自噬体输送到溶酶体，从那里 PNP 被胞吐出来。我们利用来自这些实验的数据进行生物动力学建模，其中包含与 PNP 的内化和细胞内分布、自噬、PNP 的溶酶体胞吐作用相关的过程，以及扩展我们之前对 PNP 的 AEC 处理的几种假定作用机制。结果表明，PNP 进入 AEC、随后通过胞质 PNP 激活自噬、PNP 在溶酶体中的积累以及溶酶体胞吐作用与拟议的调节机制交织在一起。