Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model

Our plain-English summary of Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model, by D.K. Lee, S. Jeon, Y. Han, et al (ACS Nano, 2018).

The study

• Authors: D.K. Lee, S. Jeon, Y. Han, S.H. Kim, S. Lee, I.J. Yu, K.S. Song, A. Kang, W.S. Yun, S.M. Kang, Y.S. Huh, W.S. Cho
• Journal: ACS Nano
• Published: 2018;12(11):10867-10879
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The qualitative and quantitative evaluation of the physicochemical parameters associated with the pathogenicity of high-aspect-ratio nanomaterials is important for comprehensive regulation efforts and safety-by-design approaches. Here, we report quantitative data on the correlations between the rigidity of these nanomaterials and toxicity endpoints in vitro and in vivo. As measured by new ISO standards published in 2017, rigidity shows a strong positive correlation with inflammogenic potential, as indicated by inflammatory cell counts and IL-1β (a biomarker for frustrated phagocytosis) levels in both the acute and chronic phases. In vitro experiments using differentiated THP-1 cells find that only highly rigid multiwalled carbon nanotubes (MWCNTs) and asbestos fibers lead to piercing and frustrated phagocytosis. Thus, this study suggests a bending ratio of 0.97 and a static bending persistence length of 1.08 as threshold rigidity values for asbestos-like pathogenicity. However, additional research using MWCNTs with rigidity values that lie between those of non-inflammogenic ( Db = 0.66 and SBPL = 0.87) and inflammogenic fibers ( Db = 0.97 and SBPL = 1.09) is required to identify more accurate threshold values, which would be useful for comprehensive regulation and safety-by-design approaches based on MWCNTs.

In plain English

This was an experimental study in mice combined with cell-culture work, testing whether the rigidity of high-aspect-ratio nanomaterials predicts asbestos-like pleural inflammation. Eight long fibre types were injected into the pleural space of ICR mice: one carbon nanofibre, four tangled multi-walled carbon nanotubes (MWCNTs), one long rigid MWCNT (CNTlong1, Mitsui & Co.), and UICC amosite and crocidolite asbestos. Rigidity was measured as bending ratio (Db) and static bending persistence length (SBPL) following ISO/TS 11888:2017. The tangled materials had Db below 0.66 and SBPL below 0.87; CNTlong1, amosite and crocidolite had Db above 0.97 and SBPL above 1.09. Twenty-four hours after injection the rigid materials caused greater increases in total cells, macrophages, granulocytes, total protein, IL-1 beta and IL-6 than the tangled materials; at four weeks only the rigid materials produced large granulomas with collagen deposition on the visceral and parietal pleura. In cultured THP-1 macrophages, only the rigid MWCNT and the asbestos fibres pierced cells and caused frustrated phagocytosis. The authors proposed Db 0.97 and SBPL 1.08 as threshold rigidity values.

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 (single intrapleural injection in mice, acute 24 h and chronic 4 week endpoints) together with in vitro experiments in differentiated THP-1 macrophages
• Who was studied: Six-week-old female ICR mice (4 per group for pleural inflammation, 3 per group for SEM of the chest wall, 3 per group for histology) and differentiated human THP-1 macrophage-like cells; laboratory study in the Republic of Korea
• Exposure: Eight high-aspect-ratio nanomaterials: one tangled carbon nanofibre (CNFtang1), four tangled MWCNTs (CNTtang1-CNTtang4), one long rigid MWCNT (CNTlong1, Mitsui & Co.) and UICC standard amosite and crocidolite asbestos; intrapleural doses 1, 2.5 and 5 micrograms per mouse (5 micrograms per mouse at 4 weeks), in vitro 12.5, 25 and 50 micrograms per mL
• Main results:
  • Rigidity split the materials into two groups: tangled fibres had Db below 0.66, rigid fibres (CNTlong1, amosite, crocidolite) above 0.97; SBPL was below 0.87 for tangled and above 1.09 for straight fibres
  • At 24 hours, rigid materials caused more pleural inflammation than tangled ones; granulocyte numbers at the 5 microgram per mouse dose correlated with rigidity (Pearson 0.9296 for Db, 0.8551 for SBPL)
  • IL-1 beta and IL-6 in pleural lavage fluid rose dose-dependently for all rigid materials, with only marginal increases for tangled materials; IL-1 beta at 5 micrograms per mouse correlated with rigidity (Pearson 0.9113 for Db, 0.8965 for SBPL)
  • At four weeks, granulocytes increased for all rigid materials; threshold values for granulocyte recruitment into the pleural space were Db 0.97 and SBPL 1.08 (chronic-phase correlations 0.8514 for Db and 0.8552 for SBPL)
  • At four weeks only the rigid materials (CNTlong1 and the asbestos fibres) produced large granulomas with collagen deposition on visceral and parietal pleura
  • In differentiated THP-1 cells, tangled materials rarely entered or pierced cells, whereas CNTlong1, amosite and crocidolite caused piercing and frustrated phagocytosis
  • Fibre diameter correlated positively with both rigidity measures (Pearson 0.6813 for Db and 0.6404 for SBPL); purity, length and the Raman IG/ID ratio showed no clear correlation with rigidity
• The authors' conclusion: The authors concluded that fibre rigidity was highly correlated with acute and chronic pleural inflammation and with frustrated phagocytosis and IL-1 beta production, and they suggested a Db of 0.97 and an SBPL of 1.08 as threshold values for asbestos-like pathogenicity, while stating further work is needed to refine them
• Limitations the authors state:
  • The authors state the study covered only pleural inflammation and carbon-based high-aspect-ratio nanomaterials
  • The authors note no materials were tested with rigidity between the non-inflammogenic and inflammogenic values, so the thresholds are not precise
  • The authors state that bending force measurement by atomic force microscopy could be more accurate for rigidity, but no ISO standard exists for it, so the SEM-based ISO method was used instead
  • The authors report that lymphocyte numbers were not significantly affected in a dose-dependent manner

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Biomarker, Frustrated Phagocytosis.

Related studies

• Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes — J.S. Kim, K. Lee, et al. (2011)
• 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)
• 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)
• Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes — D. Liao, Q. Wang, et al. (2018)
• 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)
• Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung — D. Crouzier, S. Follot, et al. (2010)

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