MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

Sarah S. Poulsen, Anne T. Saber, Andrew Williams, Ole Andersen, Carsten Købler, Rambabu Atluri, Maria E. Pozzebon, Stefano P. Mucelli, Monica Simion, David Rickerby, Alicja Mortensen, Petra Jackson, Zdenka O. Kyjovska, Kristian Mølhave, Nicklas R. Jacobsen, Keld A. Jensen, Carole L. Yauk, Hakan Wallin, Sabina Halappanavar, Ulla Birgitte Vogel

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Abstract

Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 mu g/mouse of a small, curled (CNTsmall, 0.8 +/- 0.1 mu m in length) or large, thick MWCNT (CNTLarge, 4 +/- 0.4 mu m in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bron-choalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNTsmall or CNTLarge were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNTLarge elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNTsmall. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNTLarge, which may eventually lead to the different responses observed at day 28. (C) 2015 The Authors. Published by Elsevier Inc.
Original languageEnglish
JournalToxicology and Applied Pharmacology
Volume284
Issue number1
Pages (from-to)16-32
Number of pages17
ISSN0041-008X
DOIs
Publication statusPublished - 2015

Bibliographical note

© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

Keywords

  • Nanotoxicology
  • In vivo
  • Toxicogenomics
  • DNA microarray
  • Acute phase response
  • ROS production

Cite this

Poulsen, Sarah S. ; Saber, Anne T. ; Williams, Andrew ; Andersen, Ole ; Købler, Carsten ; Atluri, Rambabu ; Pozzebon, Maria E. ; Mucelli, Stefano P. ; Simion, Monica ; Rickerby, David ; Mortensen, Alicja ; Jackson, Petra ; Kyjovska, Zdenka O. ; Mølhave, Kristian ; Jacobsen, Nicklas R. ; Jensen, Keld A. ; Yauk, Carole L. ; Wallin, Hakan ; Halappanavar, Sabina ; Vogel, Ulla Birgitte. / MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs. In: Toxicology and Applied Pharmacology. 2015 ; Vol. 284, No. 1. pp. 16-32.
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abstract = "Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 mu g/mouse of a small, curled (CNTsmall, 0.8 +/- 0.1 mu m in length) or large, thick MWCNT (CNTLarge, 4 +/- 0.4 mu m in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bron-choalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNTsmall or CNTLarge were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNTLarge elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNTsmall. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNTLarge, which may eventually lead to the different responses observed at day 28. (C) 2015 The Authors. Published by Elsevier Inc.",
keywords = "Nanotoxicology, In vivo, Toxicogenomics, DNA microarray, Acute phase response, ROS production",
author = "Poulsen, {Sarah S.} and Saber, {Anne T.} and Andrew Williams and Ole Andersen and Carsten K{\o}bler and Rambabu Atluri and Pozzebon, {Maria E.} and Mucelli, {Stefano P.} and Monica Simion and David Rickerby and Alicja Mortensen and Petra Jackson and Kyjovska, {Zdenka O.} and Kristian M{\o}lhave and Jacobsen, {Nicklas R.} and Jensen, {Keld A.} and Yauk, {Carole L.} and Hakan Wallin and Sabina Halappanavar and Vogel, {Ulla Birgitte}",
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year = "2015",
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Poulsen, SS, Saber, AT, Williams, A, Andersen, O, Købler, C, Atluri, R, Pozzebon, ME, Mucelli, SP, Simion, M, Rickerby, D, Mortensen, A, Jackson, P, Kyjovska, ZO, Mølhave, K, Jacobsen, NR, Jensen, KA, Yauk, CL, Wallin, H, Halappanavar, S & Vogel, UB 2015, 'MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs', Toxicology and Applied Pharmacology, vol. 284, no. 1, pp. 16-32. https://doi.org/10.1016/j.taap.2014.12.011

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs. / Poulsen, Sarah S.; Saber, Anne T.; Williams, Andrew; Andersen, Ole; Købler, Carsten; Atluri, Rambabu; Pozzebon, Maria E.; Mucelli, Stefano P.; Simion, Monica; Rickerby, David; Mortensen, Alicja; Jackson, Petra; Kyjovska, Zdenka O.; Mølhave, Kristian; Jacobsen, Nicklas R.; Jensen, Keld A.; Yauk, Carole L.; Wallin, Hakan; Halappanavar, Sabina; Vogel, Ulla Birgitte.

In: Toxicology and Applied Pharmacology, Vol. 284, No. 1, 2015, p. 16-32.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

AU - Poulsen, Sarah S.

AU - Saber, Anne T.

AU - Williams, Andrew

AU - Andersen, Ole

AU - Købler, Carsten

AU - Atluri, Rambabu

AU - Pozzebon, Maria E.

AU - Mucelli, Stefano P.

AU - Simion, Monica

AU - Rickerby, David

AU - Mortensen, Alicja

AU - Jackson, Petra

AU - Kyjovska, Zdenka O.

AU - Mølhave, Kristian

AU - Jacobsen, Nicklas R.

AU - Jensen, Keld A.

AU - Yauk, Carole L.

AU - Wallin, Hakan

AU - Halappanavar, Sabina

AU - Vogel, Ulla Birgitte

N1 - © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

PY - 2015

Y1 - 2015

N2 - Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 mu g/mouse of a small, curled (CNTsmall, 0.8 +/- 0.1 mu m in length) or large, thick MWCNT (CNTLarge, 4 +/- 0.4 mu m in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bron-choalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNTsmall or CNTLarge were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNTLarge elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNTsmall. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNTLarge, which may eventually lead to the different responses observed at day 28. (C) 2015 The Authors. Published by Elsevier Inc.

AB - Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 mu g/mouse of a small, curled (CNTsmall, 0.8 +/- 0.1 mu m in length) or large, thick MWCNT (CNTLarge, 4 +/- 0.4 mu m in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bron-choalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNTsmall or CNTLarge were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNTLarge elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNTsmall. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNTLarge, which may eventually lead to the different responses observed at day 28. (C) 2015 The Authors. Published by Elsevier Inc.

KW - Nanotoxicology

KW - In vivo

KW - Toxicogenomics

KW - DNA microarray

KW - Acute phase response

KW - ROS production

U2 - 10.1016/j.taap.2014.12.011

DO - 10.1016/j.taap.2014.12.011

M3 - Journal article

VL - 284

SP - 16

EP - 32

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 1

ER -