Time-dependent subcellular distribution and effects of carbon nanotubes in lungs of mice

PLoS One. 2015 Jan 23;10(1):e0116481. doi: 10.1371/journal.pone.0116481. eCollection 2015.

Abstract

Background and methods: Pulmonary deposited carbon nanotubes (CNTs) are cleared very slowly from the lung, but there is limited information on how CNTs interact with the lung tissue over time. To address this, three different multiwalled CNTs were intratracheally instilled into female C57BL/6 mice: one short (850 nm) and tangled, and two longer (4 μm and 5.7 μm) and thicker. We assessed the cellular interaction with these CNTs using transmission electron microscopy (TEM) 1, 3 and 28 days after instillation.

Results: TEM analysis revealed that the three CNTs followed the same overall progression pattern over time. Initially, CNTs were taken up either by a diffusion mechanism or via endocytosis. Then CNTs were agglomerated in vesicles in macrophages. Lastly, at 28 days post-exposure, evidence suggesting CNT escape from vesicle enclosures were found. The longer and thicker CNTs more often perturbed and escaped vesicular enclosures in macrophages compared to the smaller CNTs. Bronchoalveolar lavage (BAL) showed that the CNT exposure induced both an eosinophil influx and also eosinophilic crystalline pneumonia.

Conclusion: Two very different types of multiwalled CNTs had very similar pattern of cellular interactions in lung tissue, with the longer and thicker CNTs resulting in more severe effects in terms of eosinophil influx and incidence of eosinophilic crystalline pneumonia (ECP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Female
  • Lung / drug effects*
  • Lung / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission / methods
  • Nanotubes, Carbon / toxicity*
  • Nanotubes, Carbon / ultrastructure*
  • Particle Size
  • Pulmonary Eosinophilia / chemically induced*
  • Time Factors

Substances

  • Nanotubes, Carbon

Grants and funding

Work was supported by the Danish Centre for Nanosafety (20110092173/3) from the Danish Working Environment Research Foundation, and the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 247989 (Nanosustain) and Chemicals Management Plan of Health Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.