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Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

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Abstract

Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO2 NPs (size range 4–33 nm), two preparations of CeO2 NPs (9–36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15–240 μg/cm2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm2, in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO2 and CeO2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured nanomaterials.

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Acknowledgments

Supported by the EU-funded research project ‘Safe Nano Worker Exposure Scenarios’—SANOWORK (Grant No. FP7-280716). We thank Mr. Paul Reip (Intrinsiq Materials Ltd., Cody Technology Park, Ively Road, Farnborough—Hampshire, UK) and Prof. Lucia Migliore, University of Pisa, for CuO NPs.

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Authors and Affiliations

  1. Department of Experimental Medicine, University of Parma, Parma, Italy

    Bianca Maria Rotoli, Ovidio Bussolati, Pier Paolo Zanello, Massimiliano G. Bianchi & Rossana Visigalli

  2. Department of Pharmacological, Biological and Applied Chemical Sciences, University of Parma, Parma, Italy

    Luisana Di Cristo

  3. Institute of Science and Technology for Ceramics, National Research Council, Faenza, RA, Italy

    Anna Luisa Costa & Magda Blosi

  4. Unit of Occupational Medicine, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43125, Parma, Italy

    Enrico Bergamaschi

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  1. Bianca Maria Rotoli
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  2. Ovidio Bussolati
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  3. Anna Luisa Costa
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  4. Magda Blosi
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  5. Luisana Di Cristo
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  6. Pier Paolo Zanello
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  7. Massimiliano G. Bianchi
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  8. Rossana Visigalli
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  9. Enrico Bergamaschi
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Correspondence to Enrico Bergamaschi.

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Special Issue Editors: Candace S.-J. Tsai, Michael J. Ellenbecker

This article is part of the topical collection on Nanotechnology, Occupational and Environmental Health

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Rotoli, B.M., Bussolati, O., Costa, A.L. et al. Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages. J Nanopart Res 14, 1069 (2012). https://doi.org/10.1007/s11051-012-1069-0

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