Biokinetic Modeling of Nanoparticle Interactions with Lung Alveolar Epithelial Cells: Uptake, Intracellular Processing and Egress.

Biokinetic Modeling of Nanoparticle Interactions with Lung Alveolar Epithelial Cells: Uptake, Intracellular Processing and Egress. Am J Physiol Regul Integr Comp Physiol. 2020 Oct 21;: Authors: Chen W, D'Argenio DZ, Sipos A, Kim KJ, Crandall ED Abstract 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 cyt...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research