NADPH oxidase and mitochondria are relevant sources of superoxide anion in the oxinflammatory response of macrophages exposed to airborne particulate matter
NADPH oxidase and mitochondria are relevant sources of superoxide anion in the oxinflammatory response of macrophages exposed to airborne particulate matter
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DOI：
10.1016/j.ecoenv.2020.111186
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发表时间：
2020-12-01
影响因子：
6.8
通讯作者：
Evelson, Pablo
中科院分区：
文献类型：
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作者：
Caceres, Lourdes;Paz, Mariela L.;Evelson, Pablo
暴露在环境空气颗粒物(PM)中会增加心肺疾病的发病率和死亡率。在这种情况下，肺泡巨噬细胞由于颗粒的清除而表现出促炎和氧化反应，从而导致肺损伤。然而，连接这些通路的机制还没有完全阐明。因此，研究了暴露于残留石油飞灰(富含过渡金属的PM替代品)的原始264.7巨噬细胞的氧化炎症现象。在实验条件下，细胞活力没有受到影响，但在100mU g/mL的ROFA孵育的细胞中，观察到了促炎表型，其特征是肿瘤坏死因子-α和一氧化氮的产生增加，并伴有PM摄取。这种炎症反应似乎先于氧化还原代谢的改变，其特征是过氧化氢水平增加，GSH/GSSG比率降低，以及超氧化物歧化酶活性增加。这种情况导致对磷脂的氧化损伤增加。此外，在ROFA孵育后观察到线粒体呼吸的变化，如偶联效率和备用呼吸能力的降低，以及质子泄漏的增加。这些发现伴随着线粒体膜电位的下降。在我们的模型中，NADPH氧化酶(NOX)和线粒体被确定为超氧阴离子(O-2(中心点-))的主要来源。这些结果表明，PM暴露诱导巨噬细胞的直接激活，导致炎症，并通过NOX和线粒体增加活性氧的产生，从而削弱抗氧化防御，并可能导致线粒体功能障碍。
Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 mu g/mL, characterized by increased levels of TNF-alpha and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion (O-2(center dot-)) in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction.