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A practical approach to assess inhalation toxicity of metal oxide nanoparticles in vitro
- Source :
- Journal of Applied Toxicology. 38:160-171
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Exposure of humans to metal oxide nanoparticles (NPs) occurs mainly via air, and inhaled metal oxide NPs may generate inflammation. The aim of this study was to investigate the proinflammatory potential of six metal oxide NPs (CeO2, Mn2O3, CuO, ZnO, Co3O4 and WO3; 27–108 μg ml−1) using human primary 3-dimensional airway epithelium (MucilAir™) and dendritic cell (DC) models. Metal oxide NPs were mainly aggregated/agglomerated in the cell media, as determined by dynamic light scattering, scanning electron microscopy and differential centrifugal sedimentation. WO3 and ZnO were highly soluble, both with and without respiratory mucus. Proinflammatory signalling by the epithelium was evaluated after a 24 hour exposure by increased interleukin-6 and -8 and monocyte chemoattractant protein 1 cytokine release, which occurred only for CuO. Moreover, maturation of immature human DCs, which play a key role in the lung immune system, were evaluated by expression of surface markers HLA-DR, CD80, CD83 and CD86 after a 48 hour exposure. Only Mn2O3 consistently upregulated DC maturation markers. Furthermore, by addition of medium from metal oxide NP-exposed 3-dimensional airway cultures to metal oxide NP-exposed DC cultures, the interplay between lung epithelium and DCs was studied. Such an interplay was again only observed for Mn2O3 and in one of five DC donors. Our results show that, even when using dosages that represent very high in vivo exposure levels, up to 27 hours of constant human airway exposure, metal oxide NPs cause minimal proinflammatory effects and that epithelial cells not necessarily interfere with DC maturation upon metal oxide NP exposure. The present approach exemplifies a relevant translation towards human safety assessment. Copyright © 2017 John Wiley & Sons, Ltd.
- Subjects :
- Cell Survival
medicine.medical_treatment
Oxide
Metal Nanoparticles
Respiratory Mucosa
02 engineering and technology
010501 environmental sciences
Toxicology
Models, Biological
01 natural sciences
Proinflammatory cytokine
chemistry.chemical_compound
In vivo
Metals, Heavy
Administration, Inhalation
medicine
Humans
0105 earth and related environmental sciences
Dose-Response Relationship, Drug
Chemistry
Oxides
Dendritic Cells
Dendritic cell
021001 nanoscience & nanotechnology
Epithelium
Cytokine
medicine.anatomical_structure
Toxicity
Biophysics
Cytokines
Respiratory epithelium
0210 nano-technology
Subjects
Details
- ISSN :
- 0260437X
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Toxicology
- Accession number :
- edsair.doi.dedup.....d6d652460eb4a05d9c9ef368d0e78ae8
- Full Text :
- https://doi.org/10.1002/jat.3518