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氟化钠暴露引发了中性粒细胞胞外诱捕网的形成。

Sodium fluoride exposure triggered the formation of neutrophil extracellular traps.

机构信息

College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China; College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China.

College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China.

出版信息

Environ Pollut. 2020 Feb;257:113583. doi: 10.1016/j.envpol.2019.113583. Epub 2019 Nov 15.

Abstract

In recent years, numerous studies paid more attention to the molecular mechanisms associated with fluoride toxicity. However, the detailed mechanisms of fluoride immunotoxicity in bovine neutrophils remain unclear. Neutrophil extracellular traps (NETs) is a novel immune mechanism of neutrophils. We hypothesized that sodium fluoride (NaF) can trigger NETs activation and release, and investigate the related molecular mechanisms during the process. We exposed peripheral blood neutrophils to 1 mM NaF for 120 min in bovine neutrophils. The results showed that NaF exposure triggered NET-like structures decorated with histones and granule proteins. Quantitative measurement of NETs content correlated positively with the concentration of NaF. Mechanistically, NaF exposure increased reactive oxygen species (ROS) levels and phosphorylation levels of ERK, p38, whereas inhibiting the activities of superoxide dismutase (SOD) and catalase (CAT) compared with control neutrophils. NETs formation is induced by NaF and this effect was inhibited by the inhibitors diphenyleneiodonium chloride (DPI), U0126 and SB202190. Our findings described the potential importance of NaF-triggered NETs related molecules, which might help to extend the current understanding of NaF immunotoxicity.

摘要

近年来,大量研究关注与氟化物毒性相关的分子机制。然而,氟化物对牛中性粒细胞免疫毒性的详细机制仍不清楚。中性粒细胞胞外诱捕网(NETs)是中性粒细胞的一种新型免疫机制。我们假设氟化钠(NaF)可以触发 NETs 的激活和释放,并研究这一过程中的相关分子机制。我们将外周血中性粒细胞在牛中性粒细胞中暴露于 1mM NaF 120 分钟。结果表明,NaF 暴露引发了富含组蛋白和颗粒蛋白的 NET 样结构。NETs 含量的定量测量与 NaF 的浓度呈正相关。在机制上,与对照中性粒细胞相比,NaF 暴露增加了活性氧(ROS)水平和 ERK、p38 的磷酸化水平,而超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性则受到抑制。NaF 诱导 NETs 的形成,这种作用被二苯碘(DPI)、U0126 和 SB202190 抑制剂抑制。我们的研究结果描述了 NaF 触发的 NETs 相关分子的潜在重要性,这可能有助于扩展对 NaF 免疫毒性的现有理解。

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