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Inorganic arsenic administration suppresses human neutrophil function in vitro
Human & Experimental Toxicology ( IF 2.7 ) Pub Date : 2020-10-16 , DOI: 10.1177/0960327120966040
Md Monirul Islam 1 , Naoshi Takeyama 1
Affiliation  

Arsenic, a major environmental toxicant and pollutant, is a global public health concern. Among its many adverse effects, arsenic is immunotoxic, but its effects on human neutrophil functions are not yet well-defined. In this study, we aimed to evaluate the in vitro effects of acute low-dose NaAsO2 exposure on human polymorphonuclear neutrophils (PMNs) for 12 h on the following innate defense mechanisms: formation of neutrophil extracellular traps (NETs), production of reactive oxygen species (ROS), and phagocytosis. Phorbol myristate acetate (PMA) was added to induce NETs formation, which was quantified by measuring cell-free extracellular DNA (cf-DNA), myeloperoxidase-conjugated (MPO)-DNA and neutrophil elastase-conjugated (NE)-DNA, and confirmed by immunofluorescence labeling and imaging. Extracellular bactericidal activity by NETs was evaluated by co-culturing Escherichia coli and PMNs in the presence of a phagocytic inhibitor. Levels of NETs in the culture medium after PMA stimulation was significantly lower in PMNs pre-exposed to arsenic than those not exposed to arsenic. Immunofluorescence staining and extracellular bactericidal activity by NETs revealed similar results. Phagocytosis and ROS production by PMNs were also significantly reduced by arsenic pre-exposure. Together, our findings provide new insights in arsenic immunotoxicity and suggest how it increases susceptibility to infectious diseases in humans.



中文翻译:

无机砷给药抑制体外人中性粒细胞功能

砷是一种主要的环境毒物和污染物,是一个全球性的公共卫生问题。在其众多不利影响中,砷具有免疫毒性,但其对人类中性粒细胞功能的影响尚未明确。在本研究中,我们旨在评估急性低剂量 NaAsO 2 的体外作用暴露于人类多形核中性粒细胞 (PMN) 12 小时,具有以下先天防御机制:中性粒细胞胞外陷阱 (NET) 的形成、活性氧 (ROS) 的产生和吞噬作用。添加佛波醇肉豆蔻酸酯 (PMA) 以诱导 NET 形成,通过测量无细胞细胞外 DNA (cf-DNA)、髓过氧化物酶偶联 (MPO)-DNA 和中性粒细胞弹性蛋白酶偶联 (NE)-DNA 对其进行量化,并证实通过免疫荧光标记和成像。通过共培养大肠杆菌评估 NETs 的细胞外杀菌活性和中性粒细胞在吞噬抑制剂的存在下。PMA 刺激后培养基中 NET 的水平在预暴露于砷的 PMN 中显着低于未暴露于砷的 PMN。NETs 的免疫荧光染色和细胞外杀菌活性显示出类似的结果。砷预暴露也显着降低了 PMN 的吞噬作用和 ROS 产生。总之,我们的发现为砷免疫毒性提供了新的见解,并表明它如何增加人类对传染病的易感性。

更新日期:2020-10-17
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