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

Redox Biology

Charlie Corredor¹  Jonathan D. Posner¹  Somenath Mitra²  Megan M. Cartwright³  David K. Scoville³  Stefanie C. Schmuck³  Theodor K. Bammler³  Terrance J. Kavanagh³  Claire R. Chisholm³  Hui-Wen Wilkerson³  Zahra Afsharinejad³  William A. Altemeier⁴  Bingbing Wang⁵  Vaithiyalingam Shutthanandan⁵  Donald R. Baer⁵ 

[1] Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA;Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ 07102, USA;Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA;Department of Medicine, University of Washington, Seattle, WA 98195, USA;Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA;

关键词: Gender differences;    Glutathione;    Inflammation;    Multiwalled carbon nanotubes;    Nanotoxicology;    Oxidative stress;   

DOI  :  10.1016/j.redox.2016.08.009

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown