Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice

Our plain-English summary of Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice, by E.A. Frank, V.S. Carreira, M.E. Birch, et al (Toxicologic Pathology, 2016).

The study

• Authors: E.A. Frank, V.S. Carreira, M.E. Birch, J.S. Yadav
• Journal: Toxicologic Pathology
• Published: 2016;44(2):211-25
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Carbon nanotubes (CNTs) are emerging as important occupational and environmental toxicants owing to their increasing prevalence and potential to be inhaled as airborne particles. CNTs are a concern because of their similarities to asbestos, which include fibrous morphology, high aspect ratio, and biopersistence. Limitations in research models have made it difficult to experimentally ascertain the risk of CNT exposures to humans and whether these may lead to lung diseases classically associated with asbestos, such as mesothelioma and fibrosis. In this study, we sought to comprehensively compare profiles of lung pathology in mice following repeated exposures to multiwall CNTs or crocidolite asbestos (CA). We show that both exposures resulted in granulomatous inflammation and increased interstitial collagen; CA exposures caused predominantly bronchoalveolar hyperplasia, whereas CNT exposures caused alveolar hyperplasia of type II pneumocytes (T2Ps). T2Ps isolated from CNT-exposed lungs were found to have upregulated proinflammatory genes, including interleukin 1ß (IL-1ß), in contrast to those from CA exposed. Immunostaining in tissue showed that while both toxicants increased IL-1ß protein expression in lung cells, T2P-specific IL-1ß increases were greater following CNT exposure. These results suggest related but distinct mechanisms of action by CNTs versus asbestos which may lead to different outcomes in the 2 exposure types.

© The Author(s) 2016.

In plain English

This was an animal experiment comparing lung damage from multiwall carbon nanotubes (CNTs) and crocidolite asbestos. Male non-Swiss Albino CF-1 mice, eight per group at the start, received either material or a control liquid into the lungs by aspiration from the back of the throat. Doses were given three times a week for three weeks, and the lungs were examined five weeks later. Both materials caused granulomatous inflammation (clusters of immune cells). Both also increased collagen staining to a similar extent, but those increases were not statistically significant. Crocidolite mainly caused overgrowth of cells lining the small airways and alveolar ducts. CNTs mainly caused marked overgrowth of type II cells lining the air sacs, and CNT-exposed lungs had significantly more of these cells than crocidolite-exposed lungs. Neither material produced appreciable microscopic findings in the pleura. Type II cells from CNT-exposed lungs showed stronger activity of inflammation-related genes, including IL-1 beta, than those from crocidolite-exposed lungs. The authors concluded that CNTs produce lung changes both shared with and distinct from asbestos. They noted that their method does not fully model real exposure situations.

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 (mouse model of subchronic, repeated-dose exposure comparing two materials against a vehicle control)
• Who was studied: Six-week-old male non-Swiss Albino CF-1 mice, 8 per treatment group (vehicle control, CNT, crocidolite). One crocidolite-exposed mouse was euthanized after fighting injuries, leaving 7 in that group for most tissue analyses. Separate animals (3 per group) were used for cell isolation and gene studies.
• Exposure: High-purity multiwall carbon nanotubes (Baytubes C150HP) or crocidolite asbestos (sourced from IITRI/NIOSH), given by oropharyngeal aspiration three times a week for three weeks, followed by five weeks without exposure. The control group received the vehicle liquid (saline with 1% Pluronic F127). CNTs had an average diameter of 10.4 nm and crocidolite fibers an average diameter of 269 nm.
• Main results:
  • Both CNT- and crocidolite-exposed groups showed granulomatous inflammation.
  • CNT-exposed mice had marked, locally extensive type II pneumocyte hyperplasia.
  • Crocidolite exposure caused less severe type II pneumocyte hyperplasia and less lymphoid hyperplasia than CNT exposure.
  • Crocidolite exposure caused hyperplasia of terminal bronchioles and alveolar ducts.
  • Neither exposed group had appreciable microscopic findings in the pleura.
  • Both exposures increased collagen staining in lung tissue to a similar extent, but the increases were not statistically significant. For this analysis the crocidolite group had 6 mice.
  • The patterns of interstitial fibrosis differed: crocidolite produced more extensive peribronchial and perivascular foci, and CNTs produced nodular fibrotic foci in alveolar regions.
  • Both exposures significantly increased type II pneumocytes per alveolus compared with vehicle, and CNT-exposed lungs had significantly more than crocidolite-exposed lungs.
  • No differences in the number of dying (apoptotic) type II pneumocytes were seen between groups.
  • In isolated type II pneumocytes, CNT exposure markedly increased Cxcl1, Cxcl5, Ccl2 and IL-1 beta gene expression compared with vehicle. Crocidolite only modestly increased Cxcl1, Ccl2 and IL-1 beta, and modestly decreased Cxcl5.
  • Both exposures tended to increase IL-1 beta protein in lung cells, but CNT exposure did so more specifically in type II pneumocytes.
• The authors' conclusion: The authors concluded that CNTs appear to directly affect alveolar pneumocytes, including type II cells, producing lung pathology with features both common to and distinct from asbestos. They suggested these differences may precede or be associated with different long-term outcomes.
• Limitations the authors state:
  • Results meant to inform human health must account for limits in modeling realistic exposure. The authors used aspiration rather than inhalation, which they describe as more environmentally realistic.
  • The study aimed to compare two materials, not to assess human risk. Many uncertainty factors would apply to extrapolating the results to workers.
  • Where the CNTs and crocidolite were deposited in the lung could not be accurately monitored.
  • Extensive fibrosis may not have developed by the time of sampling, and the outbred mice used may be relatively resistant to lung fibrosis.
  • The identities of some apoptotic cells could not be confirmed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Pathology, Aspect Ratio (Length-to-diameter ratio), biopersistence, Mesothelioma, Fibrosis, Crocidolite, Inflammation.

Related studies

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• 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)
• Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs — P. Kinaret, M. Ilves, et al. (2017)
• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)
• 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)
• Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos — A.R. Murray, E.R. Kisin, et al. (2012)

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