Pardo Michal, Katra Itzhak, Schaeur James J, Rudich Yinon
Department of Earth and Planetary Sciences Weizmann Institute of Science Rehovot Israel.
Department of Geography and Environmental Development Ben-Gurion University of the Negev Beersheba Israel.
Geohealth. 2017 Mar 6;1(1):4-16. doi: 10.1002/2016GH000017. eCollection 2017 Mar.
Exposure to ambient particulate matter (PM), including PM from resuspension of soils and dusts, increases the risk for respiratory diseases. However, the exact mechanism of PM-mediated damage to the lungs remains unclear. Due to recent increases in the frequency of dust storms in many areas, we examined the cytotoxic effects of soil-dust samples collected in an arid zone in Israel on rat lung macrophages. The desert soil contains soil crusts and low levels of toxic metal content. Exposure of cells to water extracts from the dust samples caused significant reduction in the concentration of live cells and overall cell viability. The dust samples induced cell death through apoptosis, mitochondrial dysfunction, and increased mitochondrial lipid peroxidation. The dust samples generated more reactive oxygen species (ROS) compared to control-treated samples and National Institute of Standards and Technology San Joaquin Valley standard reference material. To assess whether the oxidative imbalance induced by dust extract also interferes with the antioxidant defense, we evaluated phase II detoxifying and antioxidant enzymes, which are Nrf2 classical targets. The Nrf2 transcription factor is a master regulator of cellular adaptation to stress. The dust extracts produced a significant increase in phase II detoxifying genes. This work suggests that the health-related injury observed in rat lung cells exposed to dust extracts is associated with ROS generation, mitochondrial dysfunction, mitochondrial lipid peroxidation, and cellular antioxidant imbalance. Damage to lung mitochondria may be an important mechanism by which dust-containing bacterial material induces lung injury upon inhalation.
暴露于环境颗粒物（PM），包括土壤和灰尘再悬浮产生的PM，会增加患呼吸道疾病的风险。然而，PM介导的肺损伤的确切机制仍不清楚。由于最近许多地区沙尘暴发生频率增加，我们研究了在以色列干旱地区采集的土壤灰尘样本对大鼠肺巨噬细胞的细胞毒性作用。沙漠土壤含有土壤结皮和低水平的有毒金属含量。将细胞暴露于灰尘样本的水提取物中会导致活细胞浓度和总体细胞活力显著降低。灰尘样本通过凋亡、线粒体功能障碍和线粒体脂质过氧化增加诱导细胞死亡。与对照处理的样本和美国国家标准与技术研究院圣华金河谷标准参考物质相比，灰尘样本产生了更多的活性氧（ROS）。为了评估灰尘提取物诱导的氧化失衡是否也会干扰抗氧化防御，我们评估了II期解毒和抗氧化酶，它们是Nrf2的经典靶点。Nrf2转录因子是细胞对应激适应的主要调节因子。灰尘提取物使II期解毒基因显著增加。这项工作表明，在暴露于灰尘提取物的大鼠肺细胞中观察到的与健康相关的损伤与ROS生成、线粒体功能障碍、线粒体脂质过氧化和细胞抗氧化失衡有关。肺线粒体损伤可能是含尘细菌物质吸入后诱导肺损伤的重要机制。
