Air-liquid interface exposure of in vitro lung models:improvement and application to study inhalation toxicity of aircraft-related air pollutants

10.33540/108 ◽  
2021 ◽  
Author(s):  
◽  
Ruiwen He
Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2369 ◽  
Author(s):  
Lars Leibrock ◽  
Harald Jungnickel ◽  
Jutta Tentschert ◽  
Aaron Katz ◽  
Blaza Toman ◽  
...  

Air–liquid interface (ALI) systems have been widely used in recent years to investigate the inhalation toxicity of many gaseous compounds, chemicals, and nanomaterials and represent an emerging and promising in vitro method to supplement in vivo studies. ALI exposure reflects the physiological conditions of the deep lung more closely to subacute in vivo inhalation scenarios compared to submerged exposure. The comparability of the toxicological results obtained from in vivo and in vitro inhalation data is still challenging. The robustness of ALI exposure scenarios is not yet well understood, but critical for the potential standardization of these methods. We report a cause-and-effect (C&E) analysis of a flow through ALI exposure system. The influence of five different instrumental and physiological parameters affecting cell viability and exposure parameters of a human lung cell line in vitro (exposure duration, relative humidity, temperature, CO2 concentration and flow rate) was investigated. After exposing lung epithelia cells to a CeO2 nanoparticle (NP) aerosol, intracellular CeO2 concentrations reached values similar to those found in a recent subacute rat inhalation study in vivo. This is the first study showing that the NP concentration reached in vitro using a flow through ALI system were the same as those in an in vivo study.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Amara L. Holder ◽  
Linsey C. Marr

Silver nanoparticles are one of the most prevalent nanomaterials in consumer products. Some of these products are likely to be aerosolized, making silver nanoparticles a high priority for inhalation toxicity assessment. To study the inhalation toxicity of silver nanoparticles, we have exposed cultured lung cells to them at the air-liquid interface. Cells were exposed to suspensions of silver or nickel oxide (positive control) nanoparticles at concentrations of 2.6, 6.6, and 13.2 μg cm−2(volume concentrations of 10, 25, and 50 μg ml−1) and to 0.7 μg cm−2silver or 2.1 μg cm−2nickel oxide aerosol at the air-liquid interface. Unlike a number ofin vitrostudies employing suspensions of silver nanoparticles, which have shown strong toxic effects, both suspensions and aerosolized nanoparticles caused negligible cytotoxicity and only a mild inflammatory response, in agreement with animal exposures. Additionally, we have developed a novel method using a differential mobility analyzer to select aerosolized nanoparticles of a single diameter to assess the size-dependent toxicity of silver nanoparticles.


2020 ◽  
Author(s):  
S. Runft ◽  
L. Burigk ◽  
A. Lehmbecker ◽  
K. Schöne ◽  
D. Waschke ◽  
...  

2020 ◽  
Vol 318 (6) ◽  
pp. L1158-L1164
Author(s):  
Emily Mavin ◽  
Bernard Verdon ◽  
Sean Carrie ◽  
Vinciane Saint-Criq ◽  
Jason Powell ◽  
...  

Shifts in cellular metabolic phenotypes have the potential to cause disease-driving processes in respiratory disease. The respiratory epithelium is particularly susceptible to metabolic shifts in disease, but our understanding of these processes is limited by the incompatibility of the technology required to measure metabolism in real-time with the cell culture platforms used to generate differentiated respiratory epithelial cell types. Thus, to date, our understanding of respiratory epithelial metabolism has been restricted to that of basal epithelial cells in submerged culture, or via indirect end point metabolomics readouts in lung tissue. Here we present a novel methodology using the widely available Seahorse Analyzer platform to monitor real-time changes in the cellular metabolism of fully differentiated primary human airway epithelial cells grown at air-liquid interface (ALI). We show increased glycolytic, but not mitochondrial, ATP production rates in response to physiologically relevant increases in glucose availability. We also show that pharmacological inhibition of lactate dehydrogenase is able to reduce glucose-induced shifts toward aerobic glycolysis. This method is timely given the recent advances in our understanding of new respiratory epithelial subtypes that can only be observed in vitro through culture at ALI and will open new avenues to measure real-time metabolic changes in healthy and diseased respiratory epithelium, and in turn the potential for the development of novel therapeutics targeting metabolic-driven disease phenotypes.


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