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

Journal Article · Sat Oct 01 00:00:00 EDT 2016 · Redox Biology

DOI:https://doi.org/10.1016/j.redox.2016.08.009· OSTI ID:1306683

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.

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 1306683
• Alternate ID(s): OSTI ID: 1340760
• Report Number(s): PNNL-SA-120884; S2213231716301203; PII: S2213231716301203
• Journal Information: Redox Biology, Journal Name: Redox Biology Vol. 9 Journal Issue: C; ISSN 2213-2317
• Publisher: Elsevier
• Country of Publication: Netherlands
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
Environmental Molecular Sciences Laboratory
Gender differences
Glutathione
Inflammation
Multiwalled carbon nanotubes
Nanotoxicology
Oxidative stress