Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects
Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid inter...
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doaj-54f6c5bac95240cdaec55e119b8e2c532020-12-30T00:05:46ZengMDPI AGNanomaterials2079-49912021-12-0111656510.3390/nano11010065Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse EffectsSilvia Diabaté0Lucie Armand1Sivakumar Murugadoss2Marco Dilger3Susanne Fritsch-Decker4Christoph Schlager5David Béal6Marie-Edith Arnal7Mathilde Biola-Clier8Selina Ambrose9Sonja Mülhopt10Hanns-Rudolf Paur11Iseult Lynch12Eugenia Valsami-Jones13Marie Carriere14Carsten Weiss15Karlsruhe Institute of Technology, Institute of Biological and Chemical Systems–Biological Information Processing, 76344 Eggenstein-Leopoldshafen, GermanyCEA, CNRS, IRIG, SyMMES, University Grenoble Alpes, 38054 Grenoble, FranceKarlsruhe Institute of Technology, Institute of Biological and Chemical Systems–Biological Information Processing, 76344 Eggenstein-Leopoldshafen, GermanyKarlsruhe Institute of Technology, Institute of Biological and Chemical Systems–Biological Information Processing, 76344 Eggenstein-Leopoldshafen, GermanyKarlsruhe Institute of Technology, Institute of Biological and Chemical Systems–Biological Information Processing, 76344 Eggenstein-Leopoldshafen, GermanyKarlsruhe Institute of Technology, Institute for Technical Chemistry, 76344 Eggenstein-Leopoldshafen, GermanyCEA, CNRS, IRIG, SyMMES, University Grenoble Alpes, 38054 Grenoble, FranceCEA, CNRS, IRIG, SyMMES, University Grenoble Alpes, 38054 Grenoble, FranceCEA, CNRS, IRIG, SyMMES, University Grenoble Alpes, 38054 Grenoble, FrancePromethean Particles Ltd., Nottingham NG7 3EF, UKKarlsruhe Institute of Technology, Institute for Technical Chemistry, 76344 Eggenstein-Leopoldshafen, GermanyKarlsruhe Institute of Technology, Institute for Technical Chemistry, 76344 Eggenstein-Leopoldshafen, GermanySchool of Geography Earth & Environmental Sciences (GEES), University of Birmingham (UoB), Edgbaston, Birmingham B15 2TT, UKSchool of Geography Earth & Environmental Sciences (GEES), University of Birmingham (UoB), Edgbaston, Birmingham B15 2TT, UKCEA, CNRS, IRIG, SyMMES, University Grenoble Alpes, 38054 Grenoble, FranceKarlsruhe Institute of Technology, Institute of Biological and Chemical Systems–Biological Information Processing, 76344 Eggenstein-Leopoldshafen, GermanyReliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering numerous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Membrane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For comparison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals.https://www.mdpi.com/2079-4991/11/1/65cerium dioxidezirconium-dopingtitanium dioxidenanotoxicologyalternative methods |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Silvia Diabaté Lucie Armand Sivakumar Murugadoss Marco Dilger Susanne Fritsch-Decker Christoph Schlager David Béal Marie-Edith Arnal Mathilde Biola-Clier Selina Ambrose Sonja Mülhopt Hanns-Rudolf Paur Iseult Lynch Eugenia Valsami-Jones Marie Carriere Carsten Weiss |
spellingShingle |
Silvia Diabaté Lucie Armand Sivakumar Murugadoss Marco Dilger Susanne Fritsch-Decker Christoph Schlager David Béal Marie-Edith Arnal Mathilde Biola-Clier Selina Ambrose Sonja Mülhopt Hanns-Rudolf Paur Iseult Lynch Eugenia Valsami-Jones Marie Carriere Carsten Weiss Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects Nanomaterials cerium dioxide zirconium-doping titanium dioxide nanotoxicology alternative methods |
author_facet |
Silvia Diabaté Lucie Armand Sivakumar Murugadoss Marco Dilger Susanne Fritsch-Decker Christoph Schlager David Béal Marie-Edith Arnal Mathilde Biola-Clier Selina Ambrose Sonja Mülhopt Hanns-Rudolf Paur Iseult Lynch Eugenia Valsami-Jones Marie Carriere Carsten Weiss |
author_sort |
Silvia Diabaté |
title |
Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects |
title_short |
Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects |
title_full |
Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects |
title_fullStr |
Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects |
title_full_unstemmed |
Air–Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects |
title_sort |
air–liquid interface exposure of lung epithelial cells to low doses of nanoparticles to assess pulmonary adverse effects |
publisher |
MDPI AG |
series |
Nanomaterials |
issn |
2079-4991 |
publishDate |
2021-12-01 |
description |
Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering numerous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Membrane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For comparison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals. |
topic |
cerium dioxide zirconium-doping titanium dioxide nanotoxicology alternative methods |
url |
https://www.mdpi.com/2079-4991/11/1/65 |
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