Department Biomedical and Pharmaceutical Sciences, University of Montana, Center for Environmental Health Sciences , Missoula, MT 59812 , USA.
Nanotoxicology. 2014 May;8(3):317-27. doi: 10.3109/17435390.2013.779757. Epub 2013 Mar 19.
The current study tests the hypothesis that multi-walled carbon nanotubes (MWCNT) with different surface chemistries exhibit different bioactivity profiles in vivo. In addition, the study examined the potential contribution of the NLRP3 inflammasome in MWCNT-induced lung pathology. Unmodified (BMWCNT) and MWCNT that were surface functionalised with -COOH (FMWCNT), were instilled into C57BL/6 mice. The mice were then examined for biomarkers of inflammation and injury, as well as examined histologically for development of pulmonary disease as a function of dose and time. Biomarkers for pulmonary inflammation included cytokines, mediators and the presence of inflammatory cells (IL-1β, IL-18, IL-33, cathepsin B and neutrophils) and markers of injury (albumin and lactate dehydrogenase). The results show that surface modification by the addition of the -COOH group to the MWCNT, significantly reduced the bioactivity and pathogenicity. The results of this study also suggest that in vivo pathogenicity of the BMWCNT and FMWCNT correlates with activation of the NLRP3 inflammasome in the lung.
本研究旨在验证以下假设,即具有不同表面化学性质的多壁碳纳米管(MWCNT)在体内表现出不同的生物活性谱。此外,本研究还探讨了 NLRP3 炎性体在 MWCNT 诱导的肺病理学中的潜在作用。将未经修饰的(BMWCNT)和经 -COOH 官能化的 MWCNT(FMWCNT)注入 C57BL/6 小鼠体内。然后,检查这些小鼠的炎症和损伤生物标志物,并根据剂量和时间观察其肺部疾病的发展情况。肺部炎症的生物标志物包括细胞因子、介质和炎症细胞的存在(IL-1β、IL-18、IL-33、组织蛋白酶 B 和中性粒细胞)以及损伤标志物(白蛋白和乳酸脱氢酶)。结果表明,MWCNT 表面添加 -COOH 基团的修饰显著降低了其生物活性和致病性。本研究结果还表明,BMWCNT 和 FMWCNT 的体内致病性与肺中 NLRP3 炎性体的激活相关。