Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels
Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels
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DOI：
10.1002/1873-3468.12026
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发表时间：
2016-01-01
期刊：
影响因子：
3.5
通讯作者：
Forbes, Ben
中科院分区：
文献类型：
--
作者：
Kumar, Abhinav;Dailey, Lea Ann;Forbes, Ben
迄今为止，评估吸入颗粒肺毒性的体外研究与体内结果相关性较差。我们探讨了这种差异是否反映了在大气氧浓度（21%）下培养的肺细胞与体内肺泡浓度（100mmHg，类似于13%）下培养的肺细胞的细胞适应性，以及这种差异是否减弱了细胞对纳米颗粒挑战的反应。与13%氧培养的细胞相比，在21%氧条件下，A549细胞细胞内谷胱甘肽浓度增加，对CuO纳米颗粒的耐受性增加，活性氧产生减少，转录反应减弱，细胞死亡延迟。这些数据支持了标准细胞培养条件使细胞预先适应氧化损伤的观点，并强调了在模型系统中确保常压条件以提高其预测价值的必要性。
To date, invitro studies assessing the pulmonary toxicity of inhaled particles have provided poor correlation with invivo results. We explored whether this discrepancy reflected cellular adaptations in pulmonary cells cultured under atmospheric oxygen concentrations (21%) compared with invivo alveolar concentrations (100mmHg, similar to 13%) and whether this blunted cellular responses to nanoparticle challenge. At 21% oxygen, A549 cells had augmented intracellular glutathione concentrations, with evidence of increased tolerance to CuO nanoparticles, with reduced reactive oxygen species production, blunted transcriptional responses and delayed cell death, compared to cells cultured at 13% oxygen. These data support the contention that standard cell culture conditions pre-adapt cells to oxidative insults and emphasize the necessity of ensuring normoxic conditions in model systems to improve their predictive value.