Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs

Our plain-English summary of Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs, by P. Kinaret, M. Ilves, V. Fortino, et al (ACS Nano, 2017).

The study

• Authors: P. Kinaret, M. Ilves, V. Fortino, E. Rydman, P. Karisola, A. Lähde, J. Koivisto, J. Jokiniemi, H. Wolff, K. Savolainen, D. Greco, H. Alenius
• Journal: ACS Nano
• Published: 2017;11(1):291-303
• Cited by: 72 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Carbon nanotubes (CNTs) have the potential to impact technological and industrial progress, but their production and use may, in some cases, cause serious health problems. Certain rod-shaped multiwalled CNTs (rCNTs) can, in fact, induce severe asbestos-like pathogenicity in mice, including granuloma formation, fibrosis, and even cancer. Evaluating the comparability between alternative hazard assessment methods is needed to ensure fast and reliable evaluation of the potentially adverse effects of these materials. To compare two alternative airway exposure methods, C57BL/6 mice were exposed to rCNTs by a state-of-the-art but laborious and expensive inhalation method (6.2-8.2 mg/m3, 4 h/day for 4 days) or by oropharyngeal aspiration (10 or 40 μg/day for 4 days), which is cheaper and easier to perform. In addition to histological and cytological studies, transcriptome analysis was also carried out on the lung tissue samples. Both inhalation and low-dose (10 μg/day) aspiration exposure to rCNTs promoted strong accumulation of eosinophils in the lungs and recruited also a few neutrophils and lymphocytes. In contrast, the aspiration of a high-dose (40 μg/day) rCNT caused only a mild pulmonary eosinophilia but enhanced accumulation of neutrophils in the airways. Inhalation and low-dose aspiration exposure promoted comparable giant cell formation, mucus production, and IL-13 expression in the lungs. Both exposure methods also exacerbated similar expression alterations with 154 (56.4%) differentially expressed, overlapping genes in microarray analyses. Of all differentially expressed genes, up to 80% of the activated biological functions were shared according to pathway enrichment analyses. Inhalation and low-dose aspiration elicited very similar pulmonary inflammation providing evidence that oropharyngeal aspiration is a valid approach and a convenient alternative to the inhalation exposure for the hazard assessment of nanomaterials.

In plain English

This experiment in mice compared two ways of delivering rod-like multiwalled carbon nanotubes (rCNTs) to the lungs. Asbestos itself was not tested. Female C57BL/6 mice either breathed rCNT aerosol (6.2 to 8.2 mg/m3, 4 hours a day for 4 days, in exposures from the authors' earlier published study) or had 10 or 40 micrograms of rCNTs in liquid aspirated from the back of the throat on 4 consecutive days. Inhalation and the 10-microgram aspiration dose both caused a strong buildup of eosinophils (white blood cells typical of allergic inflammation), mucus production, giant cell formation and increased IL-13 gene expression. The 40-microgram dose caused milder eosinophilia, more neutrophils, very little mucus and lower IL-13. Of genes with changed activity, 154 were shared between inhalation (178 genes) and low-dose aspiration (249 genes). The authors concluded that, with an adequately adjusted dose, aspiration could be a valid alternative to inhalation for nanomaterial hazard testing, noting that only one nanomaterial was studied.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment comparing whole-body inhalation (exposures carried out in the authors' earlier published study) with oropharyngeal aspiration of the same carbon nanotube
• Who was studied: Female C57BL/6 mice, 7 to 8 weeks old, studied in Finland; group sizes for lung-wash cell counts were 8 to 11
• Exposure: Rod-like multiwalled carbon nanotubes (rCNTs, from Mitsui & Co.). Inhaled as an aerosol at 6.2 to 8.2 mg/m3 for 4 hours a day on 4 consecutive days, or aspirated at 10 or 40 micrograms per mouse in 50 microliters of liquid on 4 consecutive days. Mice were killed 24 hours after the last exposure.
• Main results:
  • Inhalation decreased macrophages, slightly increased neutrophils and lymphocytes, and caused a large influx of eosinophils into the lungs
  • Low-dose (10 micrograms) aspiration caused allergic-type lung inflammation comparable to inhalation, with strong eosinophilia
  • High-dose (40 micrograms) aspiration decreased macrophages, slightly increased lymphocytes, and moderately increased neutrophils and eosinophils
  • Low-dose aspiration produced substantial mucus-cell overgrowth (goblet cell hyperplasia); high-dose aspiration produced only very minor mucus production
  • Inhalation triggered strong IL-13 expression in lung tissue; high-dose aspiration produced significantly lower IL-13 expression
  • Inhalation and low-dose aspiration produced comparable giant-cell formation of macrophages in lung wash fluid
  • 178 genes changed activity in the inhalation group and 249 in the low-dose aspiration group, each compared with controls; 154 (56.4%) of these genes were shared, 144 of them increased and 10 decreased
  • In additional functional analyses, the biological processes activated by inhalation and by aspiration were 80% the same
  • Nanotube clumps in lung tissue were larger after aspiration than after inhalation
• The authors' conclusion: The authors concluded that, when the dose is adequately adjusted, oropharyngeal aspiration could be a valid alternative to the more expensive and laborious inhalation method for assessing the lung hazards of nanomaterials.
• Limitations the authors state:
  • The study examined only one type of carbon nanomaterial

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Granuloma, Fibrosis.

Related studies

• Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation — E.M. Rydman, M. Ilves, et al. (2014)
• A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor — E.M. Rydman, M. Ilves, et al. (2015)
• Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice — E.J. Park, T.O. Khaliullin, et al. (2018)
• Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice — E.A. Frank, V.S. Carreira, et al. (2016)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes — K.S. Duke, E.A. Thompson, et al. (2018)

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