Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity

Abstract

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

• Bronchoalveolar lavage fluid
• inflammation
• polyvinylpyrrolidone
• pulmonary function
• surfactant

Acknowledgements

Special thanks to Thea Golden, Helen Abramova, Chang Jiang Guo, and Pamela Scott for their support in the laboratory; as well as Don Baer and Joel Pounds at PNNL for useful discussions on particle chemistry.

Declaration of interest

This investigation was supported by the National Institute of Environmental Health Sciences (NIEHS) 1 U19ES019536-01 and the NIH Training in Environmental Toxicology 5T32ES007148. The NIEHS Centers for Nanotechnology Health Implications Research (NCNHIR) was established with the centers funded by RFA ES-09-011. These centers formed a consortium with other NIEHS funded researchers and other federal labs in the area of Nano EHS and worked together on a select set of engineered nanomaterials provided to the consortium by NIEHS. Any opinions, findings, conclusions or recommendations expressed herein are those of the author(s) and do not necessarily reflect the views of the National Institute of Environmental Health Sciences/NIH.

Supplementary material available online

Supplementary Figures S1-S11