The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis.
The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis.
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DOI：
10.1016/j.redox.2016.08.009
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发表时间：
2016-10
期刊：
影响因子：
11.4
通讯作者：
Kavanagh, Terrance J.
中科院分区：
文献类型：
--
作者：
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.
关键词：
多壁碳纳米管（MWCNTs）在其制造或纳入各种商业产品的过程中吸入可能会导致肺部炎症，纤维化和氧化应激。一些工人可能更容易受到这些影响，因为他们合成主要抗氧化剂和免疫系统调节剂谷胱甘肽（GSH）的能力不同。因此，在这项研究中，我们研究了GSH合成和性别对C57 BL/6小鼠MWCNT诱导的肺部炎症的影响。谷胱甘肽合成受损，通过遗传操作Gclm，修饰亚基的谷氨酸半胱氨酸连接酶，在谷胱甘肽合成的限速酶。在吸入25 μg MWCNT后24小时，所有雄性小鼠的肺部均出现嗜中性粒细胞，无论Gclm基因型如何。然而，雌性小鼠中度（Gclm杂合子）和严重（Gclm无效）GSH缺乏症显着减少嗜中性粒细胞。我们没有发现MWCNT诱导的氧化应激的迹象，反映在肺组织和上皮衬里液，3-硝基酪氨酸形成，或改变的mRNA或蛋白质表达的几个氧化还原反应酶的GSH含量。我们的研究结果表明，谷胱甘肽缺乏的雌性小鼠是唯一容易受到一个减弱的中性粒细胞反应。如果同样的影响发生在人类，谷胱甘肽缺乏的妇女制造多壁碳纳米管可能会在更大的风险受损的嗜中性粒细胞依赖清除多壁碳纳米管从肺。相比之下，男性可能有有效的嗜中性粒细胞依赖性清除，但无论其GSH水平如何，都可能有患肺嗜中性粒细胞的风险。我们研究性别和谷胱甘肽水平如何改变碳纳米管诱导的肺毒性。无论谷胱甘肽水平如何，碳纳米管都会诱导雄性小鼠的嗜中性粒细胞。雌性小鼠谷胱甘肽水平低可减少碳纳米管诱导的嗜中性粒细胞增多症。低铁碳纳米管不诱导氧化或硝化应力。
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. We study how sex and glutathione levels alter carbon nanotube-induced lung toxicity. Carbon nanotubes induce neutrophilia in male mice, regardless of glutathione levels. Low glutathione levels in female mice reduce carbon nanotube-induced neutrophilia. Low-iron carbon nanotubes do not induce oxidative or nitrative stress.
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影响因子：
10.4
作者：
Bonner JC;Silva RM;Taylor AJ;Brown JM;Hilderbrand SC;Castranova V;Porter D;Elder A;Oberdörster G;Harkema JR;Bramble LA;Kavanagh TJ;Botta D;Nel A;Pinkerton KE
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2.3
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影响因子：
10.6
作者：
Franklin, Christopher C.;Backos, Donald S.;Mohar, Isaac;White, Collin C.;Forman, Henry J.;Kavanagh, Terrance J.
通讯作者：
Kavanagh, Terrance J.