Multi-walled carbon nanotubes activate and shift polarization of pulmonary macrophages and dendritic cells in an in vivo model of chronic obstructive lung disease

Abstract

With substantial progress of nanotechnology, there is rising concern about possible adverse health effects related to inhalation of nanomaterials, such as multi-walled carbon nanotubes (MWCNT). In particular, individuals with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD), may potentially be more susceptible to adverse health effects related to inhaled MWCNT. Hazard assessment of such inhaled nanomaterials therefore requires timely clarification. This was assessed in this study using a mouse model of COPD by exposing animals to 0.08 µg/cm² of MWCNT administered by intratracheal instillation. Treatment with MWCNT induced an accumulation of alveolar macrophages (AMφ) in bronchoalveolar lavage fluid (BALF) in COPD mice that increased from 24 h to 7 d. In COPD mice, MWCNT induced a dynamic shift in macrophage polarization as measured by expression of CD38 and CD206, and increased AMφ and lung parenchyma macrophage (LPMΦ) activation with upregulation of co-stimulatory markers CD40 and CD80. Moreover, MWCNT treatment increased the frequencies of pulmonary dendritic cells (DC), leading to an expansion of the CD11b⁺CD103⁻ DC subset. Although MWCNT did not trigger lung functional or structural changes, they induced an increased expression of the muc5AC transcript in mice with COPD. Our data provide initial evidence that inhaled MWCNT affect the pulmonary mucosal immune system by altering the numbers, phenotype, and activation status of antigen-presenting cell populations. Extrapolating these in vivo mouse findings to human pulmonary MWCNT exposure, caution is warranted in limiting exposure when handling inhalable nanofibers.

Keywords:

• Multi-walled carbon nanotubes
• chronic obstructive pulmonary disease
• lung function
• morphometry
• macrophages
• dendritic cells
• neutrophils
• inflammation

Acknowledgments

The authors would like to thank the Microscopy Imaging Center (MIC) of the University of Bern for the electron microscopy sample preparation and for the performance of microscopy with devices supported by the MIC. Furthermore, we are very grateful to Prof. Phil Stumbles (University of Western Australia) for critical proofreading of the manuscript.

Disclosure statement

The authors report no competing interests.

Availability of data and material

All data generated or analyzed during this study are included in this published article (and its additional files).

Author contributions

S.B. performed all experiments. S.S., C.W., S.A.T. and B.H. assisted in stereology experiments. A.A.A. and M.P.A. assisted in experimental work. C.v.G. and F.B. designed and supervised the project. P.W. and all authors contributed to the design of the study, the discussion, and manuscript preparation.

Additional information

Funding

This study was supported by Lungenliga Schweiz [Project No. 2014-15], Mobiliar Jubiläumsstiftung, and by Competence Center for Materials Science and Technology CCMX Materials Challenge NanoScreen.