Exposure to silver nanospheres leads to altered respiratory mechanics and delayed immune response in an in vivo Murine model

Title: Exposure to silver nanospheres leads to altered respiratory mechanics and delayed immune response in an in vivo Murine model
Authors: Botelho, D
Leo, BF
Massa, C
Sarkar, S
Tetley, T
Chung, KF
Chen, S
Ryan, MP
Porter, A
Atochina-Vasserman, EN
Zhang, J
Schwander, S
Gow, AJ
Item Type: Journal Article
Abstract: Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.
Issue Date: 26-Mar-2018
Date of Acceptance: 26-Feb-2018
URI: http://hdl.handle.net/10044/1/60777
DOI: https://dx.doi.org/10.3389/fphar.2018.00213
ISSN: 1663-9812
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Pharmacology
Volume: 9
Copyright Statement: © 2018 Botelho, Leo, Massa, Sarkar, Tetley, Chung, Chen, Ryan, Porter, Atochina-Vasserman, Zhang, Schwander and Gow. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY - https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Natural Environment Research Council (NERC)
National Institutes of Health
Royal Academy Of Engineering
Funder's Grant Number: NE/H012893/1
H50669
MMRE_P56611
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
silver nanoparticles
lung
pulmonary function
surfactant
inflammation
nanoparticles
PULMONARY SURFACTANT
LUNG INFLAMMATION
NANOPARTICLES
VITRO
INJURY
MICE
1115 Pharmacology And Pharmaceutical Sciences
Publication Status: Published
Article Number: 213
Online Publication Date: 2018-03-26
Appears in Collections:Faculty of Engineering
Materials
National Heart and Lung Institute
Airway Disease
Faculty of Medicine
Faculty of Natural Sciences



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