Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

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 salin...

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Main Authors: Botelho, Danielle, Leo, Bey Fen, Massa, Christopher, Sarkar, Srijata, Tetley, Terry, Chung, Kian F., Chen, Shu, Ryan, Mary P., Porter, Alexandra, Atochina-Vasserman, Elena N., Zhang, Junfeng, Schwander, Stephan, Gow, Andrew J.
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Published: Frontiers Media 2018
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Online Access:http://eprints.um.edu.my/22300/
https://doi.org/10.3389/fphar.2018.00213
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spelling my.um.eprints.223002019-09-11T08:57:38Z http://eprints.um.edu.my/22300/ Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model Botelho, Danielle Leo, Bey Fen Massa, Christopher Sarkar, Srijata Tetley, Terry Chung, Kian F. Chen, Shu Ryan, Mary P. Porter, Alexandra Atochina-Vasserman, Elena N. Zhang, Junfeng Schwander, Stephan Gow, Andrew J. R Medicine 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. Frontiers Media 2018 Article PeerReviewed Botelho, Danielle and Leo, Bey Fen and Massa, Christopher and Sarkar, Srijata and Tetley, Terry and Chung, Kian F. and Chen, Shu and Ryan, Mary P. and Porter, Alexandra and Atochina-Vasserman, Elena N. and Zhang, Junfeng and Schwander, Stephan and Gow, Andrew J. (2018) Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model. Frontiers in Pharmacology, 9. p. 213. ISSN 1663-9812 https://doi.org/10.3389/fphar.2018.00213 doi:10.3389/fphar.2018.00213
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Botelho, Danielle
Leo, Bey Fen
Massa, Christopher
Sarkar, Srijata
Tetley, Terry
Chung, Kian F.
Chen, Shu
Ryan, Mary P.
Porter, Alexandra
Atochina-Vasserman, Elena N.
Zhang, Junfeng
Schwander, Stephan
Gow, Andrew J.
Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model
description 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.
format Article
author Botelho, Danielle
Leo, Bey Fen
Massa, Christopher
Sarkar, Srijata
Tetley, Terry
Chung, Kian F.
Chen, Shu
Ryan, Mary P.
Porter, Alexandra
Atochina-Vasserman, Elena N.
Zhang, Junfeng
Schwander, Stephan
Gow, Andrew J.
author_facet Botelho, Danielle
Leo, Bey Fen
Massa, Christopher
Sarkar, Srijata
Tetley, Terry
Chung, Kian F.
Chen, Shu
Ryan, Mary P.
Porter, Alexandra
Atochina-Vasserman, Elena N.
Zhang, Junfeng
Schwander, Stephan
Gow, Andrew J.
author_sort Botelho, Danielle
title Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model
title_short Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model
title_full Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model
title_fullStr Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model
title_full_unstemmed Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model
title_sort exposure to silver nanospheres leads to altered respiratory mechanics and delayed immune response in an in vivo murine model
publisher Frontiers Media
publishDate 2018
url http://eprints.um.edu.my/22300/
https://doi.org/10.3389/fphar.2018.00213
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