Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice

Our plain-English summary of Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice, by F.A. Murphy, C.A. Poland, R. Duffin, et al (Nanotoxicology, 2013).

The study

• Authors: F.A. Murphy, C.A. Poland, R. Duffin, K. Donaldson
• Journal: Nanotoxicology
• Published: 2013;7(6):1157-67
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Carbon nanotubes (CNT) are fibre-like nanomaterials whose structural similarity to asbestos has raised concerns that they may also pose a mesothelioma hazard. The objective of this study was to examine the inflammatory potential of three CNT samples of differing length on the lungs and pleural cavity following introduction into the airspaces of mice.

Results: Aspiration of the two short/tangled and one long CNT sample into the lungs of mice resulted in a length-dependent inflammatory response at 1 week, i.e., only the long CNT sample caused acute neutrophilic inflammation in bronchoalveolar lavage at 1 week and progressive thickening of the alveolar septa. The authors also report length-dependent inflammatory responses in the pleural lavage after exposure only to the long CNT. The inflammatory response in the pleural cavity to long fibres and the appearance of lesions along the chest wall and diaphragm was not present at 1 week and only evident by 6 weeks post-exposure.

Conclusion: Length-dependent pathogenicity is a feature of asbestos and the results presented in this study demonstrate similar length-dependent pathogenicity of CNT in the lungs and pleural space following airspace deposition. The data support the contention that long CNT reach the pleura from the airspaces, and that they are retained at the parietal pleura and cause inflammation and lesion development. The parietal pleura is the site of origin of mesothelioma and inflammation is considered to be a process involved in asbestos carcinogenesis and so the data support the contention that CNT may pose an asbestos-like mesothelioma hazard.

In plain English

This was an animal experiment in which C57/Bl6 mice received one of three multiwalled carbon nanotube (CNT) samples by pharyngeal aspiration into the lungs: two short samples (NTshort, NTtang) and one long sample (NTlong, mean length about 36 micrometres, 84.26% of fibres longer than 15 micrometres). Lungs and the pleural cavity were lavaged at 1 and 6 weeks, and the chest wall and diaphragm examined by electron and light microscopy (three mice per treatment group for tissue analysis). Only NTlong produced a significant rise in bronchoalveolar lavage granulocytes and LDH at 1 week; these had returned to vehicle control levels by 6 weeks, while lung sections at 6 weeks showed extensive interstitial thickening and collagen deposition with NTlong. In the pleural lavage, NTlong caused a small significant granulocyte increase at 1 week and, at 6 weeks, about 10 million cells compared with about 2 million in controls, plus foreign body giant cells, raised LDH and protein, and cellular lesions on the chest wall and diaphragm. The authors concluded that CNT elicit a length-dependent inflammatory response in lungs and pleura, supporting a possible asbestos-like mesothelioma hazard.

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 pharyngeal aspiration study with 1- and 6-week timepoints)
• Who was studied: C57/Bl6 mice, with three mice per treatment group used for tissue analysis; laboratory study in Edinburgh, UK
• Exposure: Three multiwalled carbon nanotube samples aspirated into the lungs: NTshort (diameter 25.7 nm, length 1-2 micrometres), NTtang (14.84 nm, 1-5 micrometres) and NTlong (165.02 nm, mean length 36 micrometres, 84.26% of fibres longer than 15 micrometres), suspended in saline with 0.5% bovine serum albumin
• Main results:
  • In bronchoalveolar lavage at 1 week, only NTlong caused a significant increase in granulocytes; no inflammatory response to NTshort or NTtang was detected at 1 or 6 weeks in any assay
  • The lung response to NTlong (cell counts and LDH) had resolved by 6 weeks
  • Lung histology at 6 weeks showed extensive interstitial thickening and alveolar remodelling only with NTlong
  • In pleural lavage at 1 week, only NTlong caused a small but significant granulocyte increase (total cell number unchanged)
  • At 6 weeks, pleural lavage total cells were about 10 million in NTlong-treated mice versus about 2 million in controls and the short CNT groups
  • Foreign body giant cells appeared at 6 weeks in pleural lavage of NTlong-treated mice only
  • Cellular aggregates on the parietal pleura of the chest wall were found in all three NTlong-treated mice, on both sides; control, NTshort and NTtang mice had a continuous flat mesothelium
  • Lesion area on the diaphragm was significantly greater in NTlong-treated mice than in control, NTshort and NTtang mice
  • CNT were found in diaphragm sections only in NTlong-treated mice, which the authors took as confirming translocation from lung to pleural space
  • The authors calculated a human equivalent steady-state airborne exposure of 200 micrograms per cubic metre corresponding to the 50 microgram dose given to the mice (printed as 'mg' where the micro symbol was lost)
• The authors' conclusion: The authors concluded that CNT produced a length-dependent inflammatory response in the lungs and pleura after pharyngeal aspiration, that long fibres translocated to and were retained at the parietal pleura with inflammation and fibrotic lesion development, and that the data support the contention that long CNT fibres may pose a mesothelioma risk.
• Limitations the authors state:
  • The authors state the human equivalent exposure concentration is only indicative because of several assumptions about deposited dose, clearance and aerodynamic diameter
  • Fibre number, the preferred metric for fibres, could not be counted in the CNT samples, so mass was used instead
  • The authors state this small-scale mouse study cannot confidently be extrapolated to workplace mesothelioma risk

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Deposition, Mesothelioma, Pleural Cavity, Bronchoalveolar Lavage (BAL), Diaphragm, Pleura, Parietal Pleura.

Related studies

• Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura — F.A. Murphy, C.A. Poland, et al. (2011)
• Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma — K. Donaldson, F.A. Murphy, et al. (2010)
• The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells — F.A. Murphy, A. Schinwald, et al. (2012)
• 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)
• Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes — D. Liao, Q. Wang, 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)

Browse more research in Nanotoxicology, or return to medical research.