A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice

Our plain-English summary of A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice, by E.J. Park, J. Roh, S.N. Kim, et al (Archives of Toxicology, 2011).

The study

• Authors: E.J. Park, J. Roh, S.N. Kim, M.S. Kang, Y.A. Han, Y. Kim, J.T. Hong, K. Choi
• Journal: Archives of Toxicology
• Published: 2011;85(9):1121-31
• Cited by: 70 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.

In plain English

This laboratory experiment in mice tested carbon nanotubes, not asbestos. The authors placed one dose of single-walled carbon nanotubes (100 micrograms per kilogram) into the windpipes of male ICR mice, 16 per time point. Control mice (4 per time point) received the same liquid without nanotubes. Mice were examined 1, 7, 14 and 28 days later. Total lung-wash cells were 1.7, 3.9, 4.8 and 3.2 times control levels at Days 1, 7, 14 and 28; the rise was not statistically significant at Day 1 but was by Day 7. The inflammation signals IL-1 beta, TNF-alpha and IL-6 rose at Day 1 and stayed raised. Fibrosis (scarring) seen under the microscope peaked at Day 7 and lessened with time. By Day 28 the lesions were almost completely resolved, but TGF-beta, collagen and p53 were still raised. Lung mesothelin, a protein over-produced in mesothelioma, stayed raised to Day 28. The study did not examine mesothelioma itself. Two of 64 treated mice died on Day 3. The authors concluded that a single instillation may induce early lung fibrosis and subchronic tissue damage.

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: a single intratracheal instillation (liquid placed directly into the windpipe) of single-walled carbon nanotubes in mice. Groups were killed and examined at Days 1, 7, 14 and 28 and compared with vehicle-treated controls.
• Who was studied: Male 6-week-old ICR mice from Orient Bio Inc., Korea. There were 16 treated mice per time point (64 in all) and 4 vehicle-control mice per time point. Samples from the 16 mice were pooled into four test samples (n = 4). Histopathology used six mice per group.
• Exposure: Single-walled carbon nanotubes (ASP-100F, Hanhwa Nanotech, Korea): about 10% metal content by weight, 1.2 nm in diameter, 2 to 10 micrometres long. They were dispersed in water with sodium dodecyl sulfate and given as one intratracheal dose of 100 micrograms per kilogram. Average length in suspension was 0.76 micrometres. No asbestos was tested.
• Main results:
  • In treated mice, total cells in lung-wash (BAL) fluid were 1.7-fold, 3.9-fold, 4.8-fold and 3.2-fold the control level at Days 1, 7, 14 and 28.
  • The increase in total lung-wash cells in treated mice was not statistically significant at Day 1 but was significant by Day 7, compared with controls.
  • In treated mice, the neutrophil share of lung-wash cells peaked at 8.41 plus or minus 0.01% at Day 1.
  • In treated mice, lymphocytes made up 0.7%, 1.8%, 3.4% and 2.1% of lung-wash cells at Days 1, 7, 14 and 28, compared with 0.4% in controls.
  • In lung-wash fluid of treated mice, IL-1 beta, TNF-alpha and IL-6 rose 3.2-fold, 2.7-fold and 5.2-fold relative to control at Day 1. They remained at similar levels through the experiment.
  • TGF-beta in lung-wash fluid of treated mice was 103.3, 146.2, 106.9 and 117.6 pg/ml at Days 1, 7, 14 and 28, compared with 7.2 pg/ml in controls.
  • In treated mice, collagen peaked at 16.5 ng/ml in lung-wash fluid at Day 14 and at 928.7 ng/ml in blood at Day 7. Control levels were 2.81 ng/ml in lung-wash fluid and 659.59 ng/ml in blood.
  • In treated mice, the share of B cells among blood lymphocytes was 85.80%, 70.33% and 62.80% at Days 7, 14 and 28, compared with 59.03% in controls.
  • Fibrotic lesions in the lungs of treated mice peaked at Day 7, and their severity decreased with time.
  • At Day 28 the fibrotic lesions in treated mice were almost completely resolved, but TGF-beta, collagen and p53 were still up-regulated.
  • In lung tissue of treated mice, the apoptosis-related proteins p53 and caspase-3 peaked at Day 7. The inflammatory proteins COX-2 and iNOS peaked at Day 14.
  • In lung tissue of treated mice, the tissue damage-related proteins COL1A1, MMP-2, MMP-9 and mesothelin were markedly increased up to Day 28.
  • Two of the 64 treated mice died on Day 3. One death was attributed to pigmented histiocytes and the other to a hemorrhage in the lung.
• The authors' conclusion: The authors suggested that a single intratracheal instillation of single-walled carbon nanotubes may induce early lung fibrosis and subchronic tissue damage.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Mesothelioma, Cytokine, Collagen, Histopathology, Macrophage, BAL Fluid, Mesothelin.

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