TY - JOUR
T1 - Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells
AU - Sweeney, Sinbad
AU - Leo, Bey Fen
AU - Chen, Shu
AU - Abraham-Thomas, Nisha
AU - Thorley, Andrew J.
AU - Gow, Andrew
AU - Schwander, Stephan
AU - Zhang, Junfeng Jim
AU - Shaffer, Milo S P
AU - Chung, Kian Fan
AU - Ryan, Mary P.
AU - Porter, Alexandra E.
AU - Tetley, Teresa D.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf® (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20 nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag+ ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P <0.01), 24 h after treatment with 25 μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf®, this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag+ ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs.
AB - Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf® (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20 nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag+ ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P <0.01), 24 h after treatment with 25 μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf®, this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag+ ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs.
KW - Lung toxicity
KW - Silver ions
KW - Silver nanoparticles
KW - Surfactant
UR - http://www.scopus.com/inward/record.url?scp=84966700436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84966700436&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2016.04.040
DO - 10.1016/j.colsurfb.2016.04.040
M3 - Article
AN - SCOPUS:84966700436
VL - 145
SP - 167
EP - 175
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
SN - 0927-7765
ER -