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Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers.
Nanotoxicology ( IF 5 ) Pub Date : 2020-02-07 , DOI: 10.1080/17435390.2020.1717007
Mary K Schubauer-Berigan 1 , Matthew M Dahm 1 , Christine A Toennis 2 , Deborah L Sammons 2 , Tracy Eye 3 , Vamsi Kodali 3 , Patti C Zeidler-Erdely 3 , Aaron Erdely 3
Affiliation  

The objective of this study was to evaluate the association between carbon nanotube and nanofiber (CNT/F) exposure and ex vivo responses of whole blood challenged with secondary stimulants, adjusting for potential confounders, in a cross-sectional study of 102 workers. Multi-day exposure was measured by CNT/F structure count (SC) and elemental carbon (EC) air concentrations. Demographic, lifestyle and other occupational covariate data were obtained via questionnaire. Whole blood collected from each participant was incubated for 18 hours with and without two microbial stimulants (lipopolysaccharide/LPS and staphylococcal enterotoxin type B/SEB) using TruCulture technology to evaluate immune cell activity. Following incubation, supernatants were preserved and analyzed for protein concentrations. The stimulant:null response ratio for each individual protein was analyzed using multiple linear regression, followed by principal component (PC) analysis to determine whether patterns of protein response were related to CNT/F exposure. Adjusting for confounders, CNT/F metrics (most strongly, the SC-based) were significantly (p < 0.05) inversely associated with stimulant:null ratios of several individual biomarkers: GM-CSF, IFN-γ, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-17, and IL-23. CNT/F metrics were significantly inversely associated with PC1 (a weighted mean of most biomarkers, explaining 25% of the variance in the protein ratios) and PC2 (a biomarker contrast, explaining 14%). Among other occupational exposures, only solvent exposure was significant (inversely related to PC2). CNT/F exposure metrics were uniquely related to stimulant responses in challenged whole blood, illustrating reduced responsiveness to a secondary stimulus. This approach, if replicated in other exposed populations, may present a relatively sensitive method to evaluate human response to CNT/F or other occupational exposures.

中文翻译:

处理碳纳米管和纳米纤维的工人的职业暴露与离体功能免疫反应之间的关联。

这项研究的目的是在对102名工人进行的横断面研究中,评估碳纳米管和纳米纤维(CNT / F)暴露与受到二次刺激剂挑战的全血的离体反应之间的关联,以适应潜在的混杂因素。通过CNT / F结构计数(SC)和元素碳(EC)空气浓度测量多日暴露。人口统计学,生活方式和其他职业协变量数据通过问卷调查获得。使用TruCulture技术评估从每个参与者收集的全血在有无两种微生物刺激剂(脂多糖/ LPS和B / SEB葡萄球菌肠毒素)的情况下孵育18小时,以评估免疫细胞活性。孵育后,保留上清液并分析蛋白质浓度。兴奋剂:使用多元线性回归分析每种蛋白质的无效应答率,然后进行主成分(PC)分析,以确定蛋白质应答模式是否与CNT / F暴露相关。调整混杂因素后,CNT / F指标(最明显的是基于SC的指标)与以下几种生物标志物的刺激物:无效比率呈显着负相关(p <0.05):GM-CSF,IFN-γ,白介素(IL)-2 ,IL-4,IL-5,IL-10,IL-17和IL-23。CNT / F指标与PC1(大多数生物标志物的加权平均值,说明蛋白质比例差异的25%)和PC2(生物标志物对比,说明14%)显着负相关。在其他职业暴露中,仅溶剂暴露是显着的(与PC2成反比)。CNT / F暴露指标与受攻击的全血中的刺激反应具有独特的相关性,说明对次级刺激的反应性降低。如果在其他暴露人群中重复使用此方法,则可能会提供一种相对敏感的方法来评估人类对CNT / F或其他职业暴露的反应。
更新日期:2020-02-07
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