Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study

Our plain-English summary of Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study, by B.N. Snyder-Talkington, C. Dong, D.W. Porter, et al (Journal of Toxicology and Environmental Health. Part a, 2016).

The study

• Authors: B.N. Snyder-Talkington, C. Dong, D.W. Porter, B. Ducatman, M.G. Wolfarth, M. Andrew, L. Battelli, R. Raese, V. Castranova, N.L. Guo, Y. Qian
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2016;79(8):352-66
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.

In plain English

In this animal experiment, male mice received one dose of multiwalled carbon nanotubes (MWCNT) at 1, 10, 40 or 80 micrograms, 120 micrograms of crocidolite asbestos, or the suspending liquid alone (control). The dose was placed at the back of the throat and breathed in. Lungs were examined 1, 6 and 12 months later. Lung-fluid markers of cell damage and inflammation rose with MWCNT dose at all three times, though damage declined after one month. Asbestos raised the damage marker at all three times and inflammatory cells at 1 and 6 months. Fibrosis scores were significantly above control for 40 and 80 micrograms MWCNT and asbestos at every time point. At 12 months the averages were 0.83, 1.85 and 2.33 on a 0 to 4 scale. Gene-activity analysis at 12 months found that MWCNT tended to favor immune, especially T-cell, pathways. Asbestos tended to favor pathways involved in reactive oxygen species production, electron transport and cancer. The authors concluded that MWCNT can cause inflammation and fibrosis up to 1 year later, possibly through different mechanisms than asbestos.

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 in mice with three parts: lung washing (bronchoalveolar lavage), lung tissue examination under the microscope, and gene-activity (mRNA microarray) analysis of lung tissue
• Who was studied: Male C57BL/J6 mice, 7 weeks old, from Jackson Laboratories. The study was planned with 8 mice per exposure group for each part at 1, 6 or 12 months after exposure, 432 mice in total. Procedures were approved by the NIOSH Animal Care and Use Committee.
• Exposure: A single pharyngeal aspiration of dispersion medium (negative control), 1, 10, 40 or 80 micrograms of multiwalled carbon nanotubes (Hodogaya MWNT-7), or 120 micrograms of crocidolite asbestos (positive control) from a mine in the Kalahari Desert, South Africa
• Main results:
  • In MWCNT-exposed mice, the lung-fluid cell-damage marker (LDH activity) and inflammatory cells (PMN) increased significantly with dose at 1, 6 and 12 months after exposure
  • In mice exposed to 10, 40 or 80 micrograms MWCNT, LDH activity decreased after 1 month
  • Asbestos-exposed mice had significantly higher LDH than control mice at every time point
  • Asbestos-exposed mice had higher inflammatory cell (PMN) values only at 1 and 6 months
  • Average fibrosis scores at 12 months were 0 (control), 0 (1 microgram MWCNT), 0.04 (10 micrograms), 0.83 (40 micrograms), 1.85 (80 micrograms) and 2.33 (120 micrograms asbestos)
  • Fibrosis scores were significantly higher than control for 40 and 80 micrograms MWCNT and for asbestos at every time point
  • No slide showed marked fibrosis; the highest score was 3+ (moderate)
  • Inflammation scores were significantly higher than control for 80 micrograms MWCNT at 1 and 6 months
  • Inflammation scores were significantly higher than control for asbestos at all time points
  • At 1 year, foreign material was seen in lungs given 40 and 80 micrograms MWCNT
  • At 1 year, asbestos caused a foreign body giant cell reaction and fibrosis
  • At 12 months, the number of genes significantly changed compared with control was 90, 293, 301 and 254 for 1, 10, 40 and 80 micrograms MWCNT, and 350 for 120 micrograms crocidolite
  • MWCNT exposure tended to favor immune-response pathways, specifically T-cell responses. Asbestos tended to favor pathways involved in reactive oxygen species production, electron transport, and cancer.
  • The authors considered it possible that MWCNT and asbestos reach fibrosis through different cellular signaling pathways
  • By the authors' reading of the lung tissue, asbestos-induced fibrosis was associated with high persistent inflammation, which did not appear to be the case for MWCNT-induced fibrosis
• The authors' conclusion: The authors concluded that MWCNT can induce lung inflammation and fibrosis up to 1 year after exposure, and that MWCNT and asbestos may reach these effects through different mechanisms
• Limitations the authors state:
  • The authors noted that whether a single bolus dose given by pharyngeal aspiration reflects lung responses to inhalation is a long-standing debate. Citing their earlier studies, they argued that it closely simulates whole body inhalation.

Topics

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

Medical terms in this study, explained in our Lexicon: Bronchoalveolar Lavage (BAL), Lactate Dehydrogenase (LDH), Histopathology, Crocidolite, BAL Fluid, Asbestos Exposure, Fibrosis.

Related studies

• Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study — J.M. Dymacek, B.N. Snyder-Talkington, et al. (2018)
• 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)
• Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons — A.A. Shvedova, N. Yanamala, et al. (2014)
• 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)
• 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)
• Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes — K.S. Duke, E.A. Thompson, et al. (2018)

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