title: Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats.
abstract: There is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 μm) and long (L-AgNWs; 10 μm) nanowires instilled into the lungs of Sprague-Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health.
authors.forename: Kian Fan
authors.identifier: 0000-0001-7101-1426
authors.initials: KF
authors.lastname: Chung
authors.forename: Joanna
authors.initials: J
authors.lastname: Seiffert
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.forename: Ioannis G
authors.identifier: 0000-0002-9572-417X
authors.initials: IG
authors.lastname: Theodorou
authors.forename: Angela Erin
authors.initials: AE
authors.lastname: Goode
authors.affiliation: Nanotechnology and Catalysis Research Centre (NANOCAT), University of Malaya , Kuala Lumpur 50603, Malaysia.
authors.forename: Bey Fen
authors.initials: BF
authors.lastname: Leo
authors.forename: Catriona M
authors.initials: CM
authors.lastname: McGilvery
authors.forename: Farhana
authors.initials: F
authors.lastname: Hussain
authors.forename: Coen
authors.initials: C
authors.lastname: Wiegman
authors.forename: Christos
authors.identifier: 0000-0003-3470-3233
authors.initials: C
authors.lastname: Rossios
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Nicholas School of Environment and Duke Global Health Institute, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Gong
authors.forename: Farid
authors.initials: F
authors.lastname: Tariq
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yufit
authors.affiliation: Department of Biological Sciences, Oxford Brookes University , Oxford OX3 OBP, United Kingdom.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Monteith
authors.affiliation: The School of Materials, The University of Manchester , Oxford Road, Manchester M13 9PL, United Kingdom.
authors.forename: Teruo
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Cambridge Advanced Imaging Centre, Department of Anatomy, University of Cambridge , Tennis Court Road, Cambridge CB2 3DY United Kingdom.
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Skepper
authors.forename: Mary P
authors.initials: MP
authors.lastname: Ryan
authors.affiliation: Nicholas School of Environment and Duke Global Health Institute, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Porter
mesh_terms: D000818:Animals; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053770:Nanowires / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012834:Silver / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D012834:Silver
keywords: alveolar epithelial cells; bronchial hyperresponsiveness; macrophages; silver nanowires; silver sulfidation; surfactant protein D