Comparison of Lung Inflammatory and Transcriptional Responses in Mice and Rats Following Pulmonary Exposure to a Fiber Paradigm-Compatible and Non-Compatible MWCNT

Our plain-English summary of Comparison of Lung Inflammatory and Transcriptional Responses in Mice and Rats Following Pulmonary Exposure to a Fiber Paradigm-Compatible and Non-Compatible MWCNT, by L.A. Saarimäki, P.H. Danielsen, K.B. Knudsen, et al (Nanomaterials, 2025).

The study

• Authors: L.A. Saarimäki, P.H. Danielsen, K.B. Knudsen, S.S. Poulsen, S. Halappanavar, H. Wolff, P.A.S. Kinaret, D. Greco, U. Vogel
• Journal: Nanomaterials
• Published: 2025;15(17)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Inhalation of multi-walled carbon nanotubes (MWCNTs) poses potential health risks due to their structural similarity to asbestos and their ability to induce chronic lung inflammation, fibrosis, and lung cancer in animal models. This study investigated the pulmonary inflammatory and transcriptomic responses of two distinct MWCNTs-NM-401 (long, rigid) and NM-403 (short, thin)-in rats and mice using intratracheal instillation at matched dose levels at two post-exposure time points. Both MWCNTs induced acute neutrophilic inflammation and dose-dependent transcriptomic alterations in both species, with NM-403 eliciting a stronger response. Transcriptomic profiling revealed a substantial overlap in differentially expressed genes across materials and species, particularly at the early time point. Fibrosis-associated genes were upregulated in both species, with more persistent expression observed in rats. Acute phase response genes, including Orosomucoid 1 and Lipocalin 2 were commonly induced, while Serum Amyloid A3 and Orosomucoid 2 were selectively upregulated in mice. Functional enrichment analyses showed conserved activation of immune and inflammatory pathways. Our findings show that even short, non-fiber-like MWCNTs can provoke potent and persistent pulmonary effects, challenging assumptions based solely on MWCNT properties. Despite differences in long-term responses, the overall inflammatory and transcriptional profiles showed strong interspecies concordance, suggesting that both rats and mice are relevant models for assessing MWCNT-induced pulmonary toxicity.

In plain English

This animal experiment, which did not involve asbestos, compared lung responses of female rats and mice to two multi-walled carbon nanotubes (MWCNTs): long, thick NM-401 and short, thin NM-403. The nanotubes were placed directly into the windpipe at two matched doses (18 or 54 µg per mouse, 180 or 540 µg per rat), and the animals were examined 1 and 28 days later. Both materials increased neutrophils, a type of inflammatory cell, in lung washings of both species at day 1. By weight, NM-403 produced the stronger response. At day 28, neutrophil levels had declined but remained elevated, more persistently in rats. Both materials changed the activity of many lung genes, with large overlap between them (314 shared genes in mice, 850 in rats), including genes linked to fibrosis and to the acute phase response. Gene changes lasted longer in rats. The study measured gene activity, not lung scarring itself. The authors concluded that even short, non-fiber-like MWCNTs can provoke potent and persistent lung effects, and that rats and mice showed a high degree of concordance.

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 intratracheal instillation of two MWCNTs at two doses, with lung inflammation and gene expression (microarray) measured 1 and 28 days after exposure. The mouse NM-401 gene data came from a previously published dataset.
• Who was studied: Female Sprague Dawley rats (7–8 weeks old) and female C57BL/6 mice (6–7 weeks old) from Taconic Europe, Denmark. After quality-control exclusions, at least four samples remained per experimental group. The total number of animals is not stated.
• Exposure: Two MWCNTs. NM-401: long and thick, diameter 67 nm, length 4048 nm, surface area 18 m2/g, described as fiber paradigm-compatible. NM-403: short and thin, diameter 12 nm, length 443 nm, surface area 135 m2/g, not fiber paradigm-compatible. Doses were 18 or 54 µg per mouse and 180 or 540 µg per rat. The authors state these approximate one and three times the estimated 40-year occupational lung burden at the NIOSH-recommended limit of 1 µg carbon/m3. Controls received the vehicle only.
• Main results:
  • Both MWCNTs significantly increased neutrophils in lung lavage fluid in both mice and rats at 1 day after exposure.
  • On a mass basis, NM-403 induced a stronger neutrophil response than NM-401.
  • By day 28, neutrophil levels had declined but remained elevated in both species, with a more persistent response in rats.
  • In rats, gene expression changes were strongest at day 1, but substantial numbers of changed genes persisted through day 28.
  • Between NM-401 and NM-403, 314 differentially expressed genes were shared in mice and 850 in rats.
  • A core set of fibrosis-related genes (Timp1, Ccl2, Ccl17, C3, Arg1) was consistently upregulated in both species.
  • In mice, Timp1 reached a log fold change of 3.50 at day 28 after high-dose NM-403.
  • In rats, C3 showed a log fold change of 5.58 and Timp1 a log fold change of 5.25.
  • In mice, the mouse-specific acute phase genes Saa3 and Orm2 rose sharply at day 1 (log fold change 5.5 and 2.5).
  • The acute phase response was more persistent in rats than in mice.
  • 78 biological pathways were significantly enriched in mice and 56 in rats, with 45 shared between the species in at least one condition.
• The authors' conclusion: The authors concluded that even short, non-fiber-like MWCNTs can provoke potent and persistent pulmonary effects, challenging assumptions based solely on MWCNT properties. They also concluded that rats and mice showed a high degree of concordance and are complementary models.
• Limitations the authors state:
  • Direct gene-by-gene comparison between species was not performed because of differences in gene annotation and microarray platforms.
  • Intratracheal instillation was used rather than inhalation, which the authors call the gold standard for risk assessment.
  • The neutrophil percentage measure has a limited dynamic range and becomes less sensitive at high levels of inflammation.
  • The authors state that further long-term studies are needed to evaluate the disease-causing potential of non-fiber paradigm-compatible MWCNTs such as NM-403.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Fibrosis, Lung Cancer.

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