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Title: The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

Abstract

Here, inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25 µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate ( Gclm heterozygous) and severe ( Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk formore » impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.« less

Authors:
 [1];  [1];  [1];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [3];  [1];  [1]
  1. Univ. of Washington, Seattle, WA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  3. New Jersey Institute of Technology, Newark, NJ (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1306683
Alternate Identifier(s):
OSTI ID: 1340760
Report Number(s):
PNNL-SA-120884
Journal ID: ISSN 2213-2317; 48689; 400412000
Grant/Contract Number:
AC05-76RL01830
Resource Type:
Journal Article: Published Article
Journal Name:
Redox Biology
Additional Journal Information:
Journal Volume: 9; Journal Issue: C; Journal ID: ISSN 2213-2317
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Environmental Molecular Sciences Laboratory; Gender differences; Glutathione; Inflammation; Multiwalled carbon nanotubes; Nanotoxicology; Oxidative stress

Citation Formats

Cartwright, Megan M., Schmuck, Stefanie C., Corredor, Charlie, Wang, Bingbing, Scoville, David K., Chisholm, Claire R., Wilkerson, Hui -Wen, Afsharinejad, Zahra, Bammler, Theodor K., Posner, Jonathan D., Shutthanandan, Vaithiyalingam, Baer, Donald R., Mitra, Somenath, Altemeier, William A., and Kavanagh, Terrance J.. The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis. United States: N. p., 2016. Web. doi:10.1016/j.redox.2016.08.009.
Cartwright, Megan M., Schmuck, Stefanie C., Corredor, Charlie, Wang, Bingbing, Scoville, David K., Chisholm, Claire R., Wilkerson, Hui -Wen, Afsharinejad, Zahra, Bammler, Theodor K., Posner, Jonathan D., Shutthanandan, Vaithiyalingam, Baer, Donald R., Mitra, Somenath, Altemeier, William A., & Kavanagh, Terrance J.. The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis. United States. doi:10.1016/j.redox.2016.08.009.
Cartwright, Megan M., Schmuck, Stefanie C., Corredor, Charlie, Wang, Bingbing, Scoville, David K., Chisholm, Claire R., Wilkerson, Hui -Wen, Afsharinejad, Zahra, Bammler, Theodor K., Posner, Jonathan D., Shutthanandan, Vaithiyalingam, Baer, Donald R., Mitra, Somenath, Altemeier, William A., and Kavanagh, Terrance J.. Sun . "The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis". United States. doi:10.1016/j.redox.2016.08.009.
@article{osti_1306683,
title = {The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis},
author = {Cartwright, Megan M. and Schmuck, Stefanie C. and Corredor, Charlie and Wang, Bingbing and Scoville, David K. and Chisholm, Claire R. and Wilkerson, Hui -Wen and Afsharinejad, Zahra and Bammler, Theodor K. and Posner, Jonathan D. and Shutthanandan, Vaithiyalingam and Baer, Donald R. and Mitra, Somenath and Altemeier, William A. and Kavanagh, Terrance J.},
abstractNote = {Here, inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25 µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous) and severe (Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.},
doi = {10.1016/j.redox.2016.08.009},
journal = {Redox Biology},
number = C,
volume = 9,
place = {United States},
year = {Sun Aug 21 00:00:00 EDT 2016},
month = {Sun Aug 21 00:00:00 EDT 2016}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.redox.2016.08.009

Citation Metrics:
Cited by: 2works
Citation information provided by
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  • Here, inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25more » µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate ( Gclm heterozygous) and severe ( Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.« less
  • Exposure of mice to single-walled carbon nanotubes (SWCNTs) induces an unusually robust pulmonary inflammatory response with an early onset of fibrosis, which is accompanied by oxidative stress and antioxidant depletion. The role of specific components of the antioxidant protective system, specifically vitamin E, the major lipid-soluble antioxidant, in the SWCNT-induced reactions has not been characterized. We used C57BL/6 mice, maintained on vitamin E-sufficient or vitamin E-deficient diets, to explore and compare the pulmonary inflammatory reactions to aspired SWCNTs. The vitamin E-deficient diet caused a 90-fold depletion of {alpha}-tocopherol in the lung tissue and resulted in a significant decline of othermore » antioxidants (GSH, ascorbate) as well as accumulation of lipid peroxidation products. A greater decrease of pulmonary antioxidants was detected in SWCNT-treated vitamin E-deficient mice as compared to controls. Lowered levels of antioxidants in vitamin E-deficient mice were associated with a higher sensitivity to SWCNT-induced acute inflammation (total number of inflammatory cells, number of polymorphonuclear leukocytes, released LDH, total protein content and levels of pro-inflammatory cytokines, TNF-{alpha} and IL-6) and enhanced profibrotic responses (elevation of TGF-{beta} and collagen deposition). Exposure to SWCNTs markedly shifted the ratio of cleaved to full-length extracellular superoxide dismutase (EC-SOD). Given that pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNT-induced inflammation may be of practical importance in optimizing protective strategies.« less
  • Arrays of multiwalled carbon nanotubes doped with phosphorous and nitrogen are synthesized using a solution of ferrocene and triphenyl-phosphine in benzylamine in conjunction with spray pyrolysis. We demonstrate that iron phosphide (Fe3P) nanoparticles act as catalysts during nanotube growth, leading to the formation of novel PN-doped multiwalled carbon nanotubes. The samples produced were examined by SEM, HRTEM and STEM, as well as high-resolution elemental analyses using EELS and EDX spectroscopy, and their chemical stability was explored by means of thermogravimetric analysis in the presence of oxygen. The results reveal striking differences when compared to other types of doped nanotubes. Thesemore » types of hetero-doped nanotubes with the underlying theory and synthesis are predicted to offer great opportunities in the fabrication of fast responsive chemical sensors.« less
  • With an average diameter of 100-150 nm, composite nanotubes of polyaniline (PANI)/multiwalled carbon nanotubes (MWNTs) containing Fe{sub 3}O{sub 4} nanoparticles (NPs) were synthesized by a two-step method. First, we synthesized monodispersed Fe{sub 3}O{sub 4} NPs (d=17.6 nm, {sigma}=1.92 nm) on the surface of MWNTs and then decorated the nanocomposites with a PANI layer via a self-assembly method. SEM and TEM images indicated that the obtained samples had the morphologies of nanotubes. The molecular structure and composition of MWNTs/Fe{sub 3}O{sub 4} NPs/PANI nanotubes were characterized by Fourier transform infrared spectra (FTIR), energy dispersive X-ray spectrometry (EDX), X-ray photoelectron spectra (XPS), X-raymore » diffraction (XRD) and Raman spectra. UV-vis spectra confirmed the existence of PANI and its response to acid and alkali. As a multifunctional material, the conductivity and magnetic properties of MWNTs/Fe{sub 3}O{sub 4} NPs/PANI composites nanotubes were also investigated. - Graphical abstract: The work on preparing nanocomposites has been too much, but few reports were about synthesizing one-dimensional nanocomposite of three different nanoscale materials. In our work, we prepared one-dimensional multiwalled carbon nanotubes/Fe{sub 3}O{sub 4} particles/polyaniline composite nanotubes and studied their conductive and magnetic properties.« less
  • This paper presents an experimental investigation on AC conductivity and dielectric behavior of carbon black reinforced high density polyethylene (HDPE-CB) and HDPE-CB filled with multiwalled carbon nanotubes (MWNTs-CB-HDPE) and Polyaniline (PAni) coated MWNTs-CB-HDPE nanocomposites. The electrical properties such as dielectric constant ({epsilon}'), dissipation factor (tan {delta}) and AC conductivity ({sigma}{sub ac}) of nanocomposites have been measured with reference to the weight fraction (0.5 and 1 wt% MWNTs), frequency (75 KHz-30 MHz), temperature (25-90 deg. C) and sea water ageing. The experimental results showed that the increased AC conductivity and dielectric constant of the nanocomposites were influenced by PAni coated MWNTsmore » in HDPE-CB nanocomposites. The value of dielectric constant and tan {delta} decreased with increasing frequency. Further more, above 5 MHz the AC conductivity increases drastically whereas significant effect on tan {delta} was observed in less than 1 MHz.« less