Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice

Tian, Furong; Habel, Nunja; Yin, Renfu; Hirn, Stephanie; Banerjee, Atrayee; Erçal, Nuran; Takenaka, Shinji; Estrada, Giovani; Kostarelos, Kostas; Kreyling, Wolfgang G.; Stoeger, Tobias

doi:10.1016/j.ejpb.2013.03.008

Cited by 14 publications

(16 citation statements)

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“…For in vitro experiments, DWCNT were suspended in medium, incubated in an ultrasonic bath and subsequently sonicated on ice for 1 min prior to use, using a Bioruptor (Diagenode, Liege, Belgium). For in vivo experiments, DWCNT were dispersed in pyrogen-free, distilled water supplemented with 1% Pluronic F-127 (Sigma-Aldrich, Germany) – an FDA approved surfactant to facilitate dispersion quality - as described earlier [58]. The average size (Z-Ave) and size distribution (represented by the polydispersity index = PdI) of nanoparticles dispersed in medium and in water was determined by photon correlation spectroscopy using a Dynamic Laser Scatter (DLS) Zetasizer Nano ZS.…”

Section: Methodsmentioning

confidence: 99%

“…with 5 × 10 4 PFU MHV-68. After 28 days, mice were either left untreated or instilled with 50 μg of spherical (CNP) or double-walled fibre-shaped carbon nanoparticles (DWCNT) per mouse as described earlier [5, 58] (NP preparation see section “Nanoparticles”). Lung tissue was harvested after 24 h for transcriptome and metabolome analysis as well as for determination of viral genomic load and for histology.…”

Section: Methodsmentioning

confidence: 99%

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Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection

et al. 2017

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BackgroundInhalation of environmental (nano) particles (NP) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. We hypothesized that NP-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage.ResultsTo test this hypothesis, we applied different NP to cells or mice latently infected with murine gammaherpesvirus 68 (MHV-68) which provides a small animal model for the study of gammaherpesvirus-pathogenesis in vitro and in vivo. In vitro, NP-exposure induced expression of the typically lytic viral gene ORF50 and production of lytic virus. In vivo, lytic viral proteins in the lung increased after intratracheal instillation with NP and elevated expression of the viral gene ORF50 could be detected in cells from bronchoalveolar lavage. Gene expression and metabolome analysis of whole lung tissue revealed patterns with striking similarities to acute infection. Likewise, NP-exposure of human cells latently infected with Epstein-Barr-Virus also induced virus production.ConclusionsOur results indicate that NP-exposure of persistently herpesvirus-infected cells – murine or human – restores molecular signatures found in acute virus infection, boosts production of lytic viral proteins, and induces an inflammatory response in the lung – a combination which might finally result in tissue damage and pathological alterations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0181-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection

et al. 2017

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“…For example, it has been shown that MWCNT induces pulmonary inflammation, granuloma, fibrosis, and mesothelioma in experimental models [26]–[30]. MWCNT could also alter the systemic immune function in mice [31]–[35], and individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT [36].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Cellular Response Induced by Multi-Walled Carbon Nanotubes Exposure in A549 Cells

Zhang

Xing

et al. 2014

PLoS ONE

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The wide application of multi-walled carbon nanotubes (MWCNT) has raised serious concerns about their safety on human health and the environment. However, the potential harmful effects of MWCNT remain unclear and contradictory. To clarify the potentially toxic effects of MWCNT and to elucidate the associated underlying mechanisms, the effects of MWCNT on human lung adenocarcinoma A549 cells were examined at both the cellular and the protein level. Cytotoxicity and genotoxicity were examined, followed by a proteomic analysis (2-DE coupled with LC-MS/MS) of the cellular response to MWCNT. Our results demonstrate that MWCNT induces cytotoxicity in A549 cells only at relatively high concentrations and longer exposure time. Within a relatively low dosage range (30 µg/ml) and short time period (24 h), MWCNT treatment does not induce significant cytotoxicity, cell cycle changes, apoptosis, or DNA damage. However, at these low doses and times, MWCNT treatment causes significant changes in protein expression. A total of 106 proteins show altered expression at various time points and dosages, and of these, 52 proteins were further identified by MS. Identified proteins are involved in several cellular processes including proliferation, stress, and cellular skeleton organization. In particular, MWCNT treatment causes increases in actin expression. This increase has the potential to contribute to increased migration capacity and may be mediated by reactive oxygen species (ROS).

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“…Rats were treated once every other day over a 15-day period (8 times for total doses of 0.25 or 0.5 mg test material/rat). The amount of DWCNT administered to the rats was approximately equivalent to the doses used in the studies by Crouzier et al (2010), Tian et al (2013), and Sager et al (2013), discussed in the “Introduction”. The corresponding dose of MWCNT-7 was half the amount of MWCNT-N that caused lung cancer and mesothelioma in rats (Suzui et al 2016).…”

Section: Experimental Designmentioning

confidence: 88%

“…They report that DWCNT administration caused an inflammatory reaction but that the inflammatory reaction was accompanied by a decrease in reactive oxygen species production in the lung. Tian et al administered 50 µg DWCNT (3.5 nm diameter, 1–10 µm length) to female BALB/cAnNCr mice by intratracheal instillation and examined the mice at 1 day, 3 days, and 7 days after instillation (Tian et al 2013). They report that DWCNT administration caused pulmonary inflammation that persisted for 7 days.…”

Section: Introductionmentioning

confidence: 99%

Comparative pulmonary toxicity of a DWCNT and MWCNT-7 in rats

et al. 2018

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Very little is known about the in vivo toxicity of inhaled double-walled carbon nanotubes (DWCNTs). In the present study, we compared the pulmonary toxicity of DWCNT to MWCNT-7, a well-known multi-walled carbon nanotube. Rats were divided into six groups: untreated, vehicle, low-dose DWCNT, high-dose DWCNT, low-dose MWCNT-7, and high-dose MWCNT-7. The test materials were administered by intra-tracheal intra-pulmonary spraying (TIPS) every other day for 15 days: the low-dose and high-dose groups were administered final total doses of 0.25 and 0.50 mg/rat of the test material. The animals were sacrificed 1 and 6 weeks after the final TIPS administration. Six weeks after the final TIPS administration, rats administered MWCNT-7 had high levels of macrophage infiltration into the lung with dense alveolar wall fibrous thickening throughout the lung; significant elevation of lactate dehydrogenase activity, alkaline phosphatase activity, and total protein concentration in the bronchioalveolar lavage fluid; an increase in the pulmonary cell PCNA index; slightly elevated levels of 8-OHdG DNA adducts in lung tissue DNA; a small but significant increase in protein concentration in the pleural cavity lavage fluid and an increase in the visceral mesothelial cell PCNA index. None of these parameters was increased in rats administered DWCNT. The primary lesion in rats administered DWCNT was scattered formation of granulation tissue containing internalized DWCNT fibers. Our data indicate that DWCNT has lower pulmonary and pleural toxicity than MWCNT-7.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2336-3) contains supplementary material, which is available to authorized users.

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Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice

Cited by 14 publications

References 47 publications

Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection

Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection

Proteomic Analysis of Cellular Response Induced by Multi-Walled Carbon Nanotubes Exposure in A549 Cells

Comparative pulmonary toxicity of a DWCNT and MWCNT-7 in rats

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