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

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, Håkan

AU - Halappanavar, Sabina

AU - Vogel, Ulla

N1 - Corrigendum to “MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs” [Toxicol. Appl. Pharmacol., 284 (2015) 16–32]

PY - 2015/4/1

Y1 - 2015/4/1

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 μg/mouse of a small, curled (CNTSmall, 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNTLarge, 4 ± 0.4 μm 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 24h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar 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.

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 μg/mouse of a small, curled (CNTSmall, 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNTLarge, 4 ± 0.4 μm 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 24h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar 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.

KW - Animals

KW - Bronchoalveolar Lavage Fluid

KW - DNA Damage

KW - Dose-Response Relationship, Drug

KW - Female

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Inflammation Mediators

KW - Inhalation Exposure

KW - Lung

KW - Mice, Inbred C57BL

KW - Nanotubes, Carbon

KW - Particle Size

KW - Pneumonia

KW - Pulmonary Fibrosis

KW - Reactive Oxygen Species

KW - Risk Assessment

KW - Surface Properties

KW - Time Factors

KW - Toxicogenetics

KW - Transcription, Genetic

U2 - 10.1016/j.taap.2014.12.011

DO - 10.1016/j.taap.2014.12.011

M3 - Journal article

C2 - 25554681

SN - 0041-008X

VL - 284

SP - 16

EP - 32

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

IS - 1

ER -