title: Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells.
abstract: 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 20nm 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), 24h after treatment with 25μg/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.
authors.affiliation: Lung Cell Biology, Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: Sinbad
authors.initials: S
authors.lastname: Sweeney
authors.affiliation: Department of Materials and London Centre for Nanotechnology, Imperial College London, London, UK; Department of Mechanical Engineering, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Bey Fen
authors.initials: BF
authors.lastname: Leo
authors.affiliation: Department of Chemistry and London Centre for Nanotechnology, Imperial College London, London, UK.
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Lung Cell Biology, Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: Nisha
authors.initials: N
authors.lastname: Abraham-Thomas
authors.affiliation: Lung Cell Biology, Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thorley
authors.affiliation: Department of Toxicology, Ernst Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gow
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, Rutgers University, Piscataway, NJ, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwander
authors.affiliation: Division of Environmental Sciences & Policy, Nicholas School of the Environment and Duke Global Health Institute,, Duke University, Durham, USA.
authors.forename: Junfeng Jim
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and London Centre for Nanotechnology, Imperial College London, London, UK.
authors.forename: Milo S P
authors.initials: MSP
authors.lastname: Shaffer
authors.affiliation: Respiratory Medicine and Experimental Studies Unit, Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: Department of Materials and London Centre for Nanotechnology, Imperial College London, London, UK.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Ryan
authors.affiliation: Department of Materials and London Centre for Nanotechnology, Imperial College London, London, UK.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Porter
authors.affiliation: Lung Cell Biology, Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK. Electronic address: t.tetley@imperial.ac.uk.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007477:Ions; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D011650:Pulmonary Alveoli / Q000473:pathology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*
chemical_list: D018836:Inflammation Mediators; D007477:Ions; D011663:Pulmonary Surfactants; D017382:Reactive Oxygen Species; D012834:Silver
keywords: Lung toxicity; Silver ions; Silver nanoparticles; Surfactant