Long-term polarization of alveolar macrophages to a profibrotic phenotype after inhalation exposure to multi-wall carbon nanotubes

PLoS One. 2018 Oct 29;13(10):e0205702. doi: 10.1371/journal.pone.0205702. eCollection 2018.

Abstract

Background: Nanomaterials are widely used in various fields. Although the toxicity of carbon nanotubes (CNTs) in pulmonary tissues has been demonstrated, the toxicological effect of CNTs on the immune system in the lung remains unclear.

Methods and finding: In this study, exposure to Taquann-treated multi-walled CNTs (T-CNTs) was performed using aerosols generated in an inhalation chamber. At 12 months after T-CNT exposure, alveolar inflammation with macrophage accumulation and hypertrophy of the alveolar walls were observed. In addition, fibrotic lesions were enhanced by T-CNT exposure. The macrophages in the bronchoalveolar lavage fluid of T-CNT-exposed mice were not largely shifted to any particular population, and were a mixed phenotype with M1 and M2 polarization. Moreover, the alveolar macrophages of T-CNT-exposed mice produced matrix metalloprotinase-12.

Conclusions: These results suggest that T-CNT exposure promoted chronic inflammation and fibrotic lesion formation in profibrotic macrophages for prolonged periods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity
  • Air Pollution / adverse effects
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Humans
  • Inhalation Exposure / adverse effects
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / pathology
  • Matrix Metalloproteinase 12 / immunology
  • Matrix Metalloproteinase 12 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nanotubes, Carbon / toxicity*
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / pathology

Substances

  • Air Pollutants
  • Nanotubes, Carbon
  • Matrix Metalloproteinase 12
  • matrix metallopeptidase 12, mouse

Grants and funding

This study was supported by the Health Sciences Research Grants H26-kagaku-ippan-003 and H29-kagakku-ippan-003) and a JSPS KAKENHI (Grant Number 16H02690). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.