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

Our plain-English summary of 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, by K. Donaldson, F.A. Murphy, R. Duffin, et al (Particle and Fibre Toxicology, 2010).

The study

• Authors: K. Donaldson, F.A. Murphy, R. Duffin, C.A. Poland
• Journal: Particle and Fibre Toxicology
• Published: 2010;7:5
• Type of article: Review
• Cited by: 606 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The unique hazard posed to the pleural mesothelium by asbestos has engendered concern in potential for a similar risk from high aspect ratio nanoparticles (HARN) such as carbon nanotubes. In the course of studying the potential impact of HARN on the pleura we have utilised the existing hypothesis regarding the role of the parietal pleura in the response to long fibres. This review seeks to synthesise our new data with multi-walled carbon nanotubes (CNT) with that hypothesis for the behaviour of long fibres in the lung and their retention in the parietal pleura leading to the initiation of inflammation and pleural pathology such as mesothelioma. We describe evidence that a fraction of all deposited particles reach the pleura and that a mechanism of particle clearance from the pleura exits, through stomata in the parietal pleura. We suggest that these stomata are the site of retention of long fibres which cannot negotiate them leading to inflammation and pleural pathology including mesothelioma. We cite thoracoscopic data to support the contention, as would be anticipated from the preceding, that the parietal pleura is the site of origin of pleural mesothelioma. This mechanism, if it finds support, has important implications for future research into the mesothelioma hazard from HARN and also for our current view of the origins of asbestos-initiated pleural mesothelioma and the common use of lung parenchymal asbestos fibre burden as a correlate of this tumour, which actually arises in the parietal pleura.

In plain English

This article was a review setting out the authors' hypothesis about how long fibres, including asbestos and multi-walled carbon nanotubes, might harm the pleura. Drawing on published studies, they argued that a fraction of all deposited particles reach the pleural space and leave through small openings (stomata) in the parietal pleura, the lining of the chest wall. They argued that long fibres cannot pass through these openings and are retained there. The review also briefly described the authors' own new mouse experiments, which were being submitted for peer review elsewhere. Long amosite asbestos and two long nanotube samples injected into the pleural space caused inflammation, while the short samples did not cause significant inflammation. Long nanotubes still caused a high level of inflammation at 7 days and were seen in granulomas on the parietal pleura on day 7. The authors suggested, as a hypothesis, that this retention initiates inflammation and pleural disease including mesothelioma. Their mouse experiments reported inflammation and granulomas, not mesothelioma. They argued that this calls into question lung fibre burden as a correlate of mesothelioma. They said further research was needed to establish how fibres reach the pleural space.

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: Review of the evidence for a hypothesis, including brief, not yet peer-reviewed descriptions of the authors' own animal experiments in mice
• Who was studied: Published studies on particles, fibres and the pleura (human autopsy and thoracoscopy studies, animal and cell studies), plus the authors' own experiments injecting fibres into the pleural space of mice. The number of mice is not given.
• Exposure: In the authors' pleural injection experiments: long and short amosite asbestos, two long multi-walled carbon nanotube samples, two short/tangled nanotube samples, and nanoparticulate carbon black as a control
• Main results:
  • In the authors' mouse pleural injection experiments, long amosite and the two long nanotube samples caused inflammation in the pleural space. All the short samples failed to cause significant inflammation.
  • In the mouse pleural experiments, inflammation from long nanotubes at 7 days was as high as at 1 day
  • Long fibres seen on day 1 after pleural injection were still visible in granulomas at the surface of the parietal pleura in mice on day 7
  • With short fibres, the thickened mesothelium seen at day 1 had returned to normal by day 7, which the authors took to suggest the short fibres had been cleared
  • In the authors' earlier peritoneal study in mice (6 months after injection of 10 μg), long nanotubes caused a florid granuloma response, while short/tangled nanotubes produced very little tissue reaction
  • Among the studies reviewed (Boutin and co-workers): when sites around the stomata of the parietal pleura were specifically sampled in 14 patients with asbestos-associated diseases, including mesothelioma, much longer fibres were found concentrated there
  • The authors' argument (not a measurement): because they regard the parietal pleura, not the lung tissue, as the site of origin of mesothelioma, they questioned the use of lung tissue fibre burden as a correlate of mesothelioma
• The authors' conclusion: The authors suggested that long fibres are retained at the parietal pleura because they cannot be cleared through the stomata. They suggested this retention initiates inflammation and pleural pathology including mesothelioma.
• Limitations the authors state:
  • The authors presented the mechanism as a hypothesis that still needs support
  • How fibres travel from the lung to the pleural space is not established
  • No inhalation study with long carbon nanotubes had yet been carried out
  • The authors' new pleural data were only briefly described and were being submitted for peer review elsewhere
  • The small, unevenly distributed stomatal sites of the parietal pleura are hard to sample for fibre burden

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelium, Parietal Pleura, Inflammation, Mesothelioma, Aspect Ratio (Length-to-diameter ratio), Pleura, Pathology, Pleural Mesothelioma.

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)
• Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice — F.A. Murphy, C.A. Poland, et al. (2013)
• 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)
• Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model — D.K. Lee, S. Jeon, et al. (2018)
• Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation — E.M. Rydman, M. Ilves, et al. (2014)
• Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf) — T. Chernova, F.A. Murphy, et al. (2017)

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