Acute toxicity of silver and carbon nanoaerosols to normal and cystic fibrosis human bronchial epithelial cells

Abstract

Inhalation of engineered nanoparticles (NP) poses a still unknown risk. Individuals with chronic lung diseases are expected to be more vulnerable to adverse effects of NP than normal subjects, due to altered respiratory structures and functions. Realistic and dose-controlled aerosol exposures were performed using the deposition chamber NACIVT. Well-differentiated normal and cystic fibrosis (CF) human bronchial epithelia (HBE) with established air–liquid interface and the human bronchial epithelial cell line BEAS-2B were exposed to spark-generated silver and carbon nanoaerosols (20 nm diameter) at three different doses. Necrotic and apoptotic cell death, pro-inflammatory response, epithelial function and morphology were assessed within 24 h after aerosol exposure. NP exposure resulted in significantly higher necrosis in CF than normal HBE and BEAS-2B cells. Before and after NP treatment, CF HBE had higher caspase-3 activity and secreted more IL-6 and MCP-1 than normal HBE. Differentiated HBE had higher baseline secretion of IL-8 and less caspase-3 activity and MCP-1 secretion compared to BEAS-2B cells. These biomarkers increased moderately in response to NP exposure, except for MCP-1, which was reduced in HBE after AgNP treatment. No functional and structural alterations of the epithelia were observed in response to NP exposure. Significant differences between cell models suggest that more than one and fully differentiated HBE should be used in future toxicity studies of NP in vitro.

Our findings support epidemiologic evidence that subjects with chronic airway diseases are more vulnerable to adverse effects of particulate air pollution. Thus, this sub-population needs to be included in nano-toxicity studies.

• Air–liquid interface
• airways
• cell death
• NACIVT
• pro-inflammatory cytokines

Acknowledgements

The authors thank L. Dümbgen and C. Strähl (Institute of Mathematical Statistics and Actuarial Science, Bern, Switzerland) for statistical analysis of the data, B. Kupferschmid (Institute of Anatomy, Bern, Switzerland) for excellent TEM sample preparation and B. Krieger (Institute of Anatomy, Bern, Switzerland) for photographic assistance. We also thank D. Egli and P. Stiegmeier (Institute of Aerosol and Sensor Technology, Windisch, Switzerland), who helped to develop and construct NACIVT.

Declaration of interest

This study was supported by the Swiss National Science Foundation, NRP 64, project no. 406440-131267. The authors report no conflicts of interest.