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

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-dependentmore » 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:
Report Number(s):
PNNL-SA-120884
Journal ID: ISSN 2213-2317; 48689; 400412000
Grant/Contract Number:
AC05-76RL01830
Type:
Published Article
Journal Name:
Redox Biology
Additional Journal Information:
Journal Volume: 9; Journal Issue: C; Journal ID: ISSN 2213-2317
Publisher:
Elsevier
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)
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
OSTI Identifier:
1306683
Alternate Identifier(s):
OSTI ID: 1340760