Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes

Our plain-English summary of Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes, by J. Xu, D.B. Alexander, M. Futakuchi, et al (Cancer Science, 2014).

The study

• Authors: J. Xu, D.B. Alexander, M. Futakuchi, T. Numano, K. Fukamachi, M. Suzui, T. Omori, J. Kanno, A. Hirose, H. Tsuda
• Journal: Cancer Science
• Published: 2014;105(7):763-9
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Multiwalled carbon nanotubes (MWCNT) have a fibrous structure similar to asbestos, raising concern that MWCNT exposure may lead to asbestos-like diseases. Previously we showed that MWCNT translocated from the lung alveoli into the pleural cavity and caused mesothelial proliferation and fibrosis in the visceral pleura. Multiwalled carbon nanotubes were not found in the parietal pleura, the initial site of development of asbestos-caused pleural diseases in humans, probably due to the short exposure period of the study. In the present study, we extended the exposure period to 24 weeks to determine whether the size and shape of MWCNT impact on deposition and lesion development in the pleura and lung. Two different MWCNTs were chosen for this study: a larger sized needle-like MWCNT (MWCNT-L; l = 8 μm, d = 150 nm), and a smaller sized MWCNT (MWCNT-S; l = 3 μm, d = 15 nm), which forms cotton candy-like aggregates. Both MWCNT-L and MWCNT-S suspensions were administered to the rat lung once every 2 weeks for 24 weeks by transtracheal intrapulmonary spraying. It was found that MWCNT-L, but not MWCNT-S, translocated into the pleural cavity, deposited in the parietal pleura, and induced fibrosis and patchy parietal mesothelial proliferation lesions. In addition, MWCNT-L induced stronger inflammatory reactions including increased inflammatory cell number and cytokine/chemokine levels in the pleural cavity lavage than MWCNT-S. In contrast, MWCNT-S induced stronger inflammation and higher 8-hydroxydeoxyguanosine level in the lung tissue than MWCNT-L. These results suggest that MWCNT-L has higher risk of causing asbestos-like pleural lesions relevant to mesothelioma development.

© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

In plain English

This animal experiment studied multiwalled carbon nanotubes (MWCNT), which the authors describe as structurally similar to asbestos; no asbestos was tested. Male F344 rats (six per group) had one of two nanotubes sprayed into the lungs 13 times over 24 weeks. One was larger and needle-like (MWCNT-L, mean length 8 micrometres). The other was smaller and formed cotton candy-like clumps (MWCNT-S, mean length 3 micrometres). Comparison groups got the dispersing agent alone or nothing. MWCNT-L reached the pleural cavity and was found in the parietal pleura in four of six rats. MWCNT-S was not found in the pleura. Where MWCNT-L lay, the pleura was thickened with collagen, and patchy mesothelial cell proliferation was seen. No tumors were found in either nanotube group's pleura or lung air sacs. MWCNT-L caused more inflammation in the pleural cavity. MWCNT-S caused more lung inflammation and raised an oxidative stress marker in the lung. The authors concluded that the larger MWCNT has greater potential to cause asbestos-like pleural lesions. They noted zinc content and rigidity, not only size and shape, may contribute.

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 (rats given repeated lung spraying of two types of multiwalled carbon nanotubes)
• Who was studied: Male F344 (Fisher 344) rats, 10 weeks old at the start, in four groups of six: untreated, dispersing agent (PF68) only, MWCNT-L, and MWCNT-S; Nagoya City University, Japan
• Exposure: Two multiwalled carbon nanotubes were used. MWCNT-L was a larger, needle-like type (mean length 8 micrometres, diameter 150 nm). MWCNT-S was a smaller type that formed cotton candy-like aggregates (mean length 3 micrometres, diameter 15 nm). They were given as 0.5 mL of a 250 micrograms per mL suspension by transtracheal intrapulmonary spraying, once every 2 weeks, 13 times over 24 weeks, for a total of 1.625 mg per rat. No asbestos was tested.
• Main results:
  • In the MWCNT-L group, the nanotubes were deposited in the parietal pleura in 4 of 6 rats. They were also found in the visceral pleura.
  • In the MWCNT-S group, the nanotubes were not found in either the parietal or the visceral pleura.
  • Pleural thickness is given as mean plus or minus SD. In MWCNT-L rats it was measured only at regions where fibers were seen.
• MWCNT-L: parietal 28.75 plus or minus 10.43 micrometres; visceral 18.92 plus or minus 10.13 micrometres. Both were a significant increase over the other groups.
• MWCNT-S: parietal 7.28 plus or minus 4.37; visceral 6.16 plus or minus 2.05.
• PF68 only: parietal 7.16 plus or minus 4.95; visceral 4.57 plus or minus 1.23.
  • No neoplastic development (tumors) was found in the parietal or visceral pleura of either MWCNT group.
  • No alveolar neoplastic proliferation (tumor growth in the lung air sacs) was found.
  • In the MWCNT-L group, patchy foci of mesothelial cell proliferation were seen in the parietal pleura. PCNA indices (a proliferation marker) were significantly increased in both parietal and visceral mesothelium. The MWCNT-S group was comparable to the PF68 group.
  • In pleural cavity lavage, MWCNT-L fibers were found: about 1 in 1800 cells was a fiber-containing macrophage. MWCNT-S was not detected. Cell numbers rose in both MWCNT groups and were significantly greater in the MWCNT-L group than in the MWCNT-S group.
  • In pleural cavity lavage fluid, levels of IP-10, RANTES, IL-2 and IL-18 were significantly higher in the MWCNT-L group than in the MWCNT-S group.
  • In lung tissue, several inflammatory cytokines and chemokines were significantly higher in the MWCNT-S group than in the MWCNT-L group. These included MIP-1 alpha, MIP2, MCP1, IL-1 beta and VEGF.
  • MWCNT-S was more potent than MWCNT-L in raising 8-hydroxydeoxyguanosine, an oxidative stress marker, in lung tissue.
  • MWCNT-L was also found outside the lung. It was seen in mediastinal, submandibular and mesentery lymph nodes, and a few fibers were seen in the liver, kidney, spleen and brain. MWCNT-S was not detected in these organs.
• The authors' conclusion: The authors concluded that MWCNT-L deposition, with fibrosis and mesothelial cell proliferation in the parietal pleura, indicates that the larger MWCNT has greater potential to induce asbestos-like pleural lesions. They also wrote that the site of deposition and its associated toxicity should be taken into account in regulating carbon nanotube exposure.
• Limitations the authors state:
  • The two nanotubes differed in more than size and shape. Chemical composition (MWCNT-L contains zinc) and rigidity may have contributed to the different effects.
  • Accurately modeling human exposure to asbestos-like fibers, and the disease that follows, is difficult in rodents. The doses used were much higher than the US NIOSH recommended exposure limit for carbon nanotubes.
  • The authors could not quantitatively analyze alveolar macrophage numbers, because most macrophages in the MWCNT-S group were degenerative or necrotic.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Translocation, Deposition, Alveoli, Pleural Cavity, Fibrosis, Visceral Pleura, Parietal Pleura, Pleura.

Related studies

• Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats — J. Xu, M. Futakuchi, et al. (2012)
• Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes — D. Liao, Q. Wang, et al. (2018)
• Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors — M. Suzui, M. Futakuchi, et al. (2016)
• 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)
• Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes — Y.J. Arnoldussen, V. Skaug, et al. (2018)
• Intraperitoneal administration of tangled multiwalled carbon nanotubes of 15 nm in diameter does not induce mesothelial carcinogenesis in rats — H. Nagai, Y. Okazaki, et al. (2013)

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