College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China.
College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China.
Poult Sci. 2022 Jan;101(1):101550. doi: 10.1016/j.psj.2021.101550. Epub 2021 Oct 20.
Fumonisin B (FB) is a common mycotoxin contamination in agricultural commodities being considered as a significant risk to human and livestock health, while the mechanism of FB immunotoxicity are less understood, especially in chicken. Given that extracellular traps as a novel defense mechanism of leukocytes play an important role against foreign matters, in this study we aimed to investigate the effects of FB on chicken heterophil extracellular traps (HETs) formation. Our result showed that FB induced HETs release in chicken heterophils observed via immunostaining, and it was concentration-dependent during 10 to 40 μM. Moreover, in 40 μM FB-exposed chicken heterophils, reactive oxygen species (ROS) level was increased, while catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity and glutathione (GSH) content were decreased. Simultaneously, FB (40 μM) activated ERK and p38 MAPK signaling pathways via increasing the phosphorylation level of ERK and p38 proteins. However, pretreatment of SB202190, U0126, and diphenyleneiodonium chloride (DPI) did not change FB-triggered ROS production and HETs formation, suggesting FB-induced HETs was a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38, and extracellular regulated protein kinases (ERK) signaling pathways-independent process. Inhibition of peptidyl arginine deiminase 4 (PAD4) enzyme and P2 × 1 receptor showed their vital role in 40 μM FB-triggered HETs. This study reported for the first time that 40 μM FB induced the release of HETs in heterophils, and it was related to ROS production, PAD4, and P2 × 1, but was independent of NADPH oxidase, p38 and ERK signaling pathways, which might provide a whole novel perspective of perceiving and understanding the role of FB in immunotoxicity.
伏马菌素 B（FB）是农业商品中常见的真菌毒素污染，被认为对人类和牲畜健康构成重大风险，而 FB 免疫毒性的机制知之甚少，特别是在鸡中。鉴于细胞外陷阱作为白细胞的一种新的防御机制，在对抗外来物质方面发挥着重要作用，本研究旨在研究 FB 对鸡嗜中性粒细胞细胞外陷阱（HETs）形成的影响。我们的结果表明，通过免疫染色观察到 FB 诱导鸡嗜中性粒细胞释放 HETs，并且在 10 至 40 μM 之间呈浓度依赖性。此外，在暴露于 40 μM FB 的鸡嗜中性粒细胞中，活性氧（ROS）水平增加，而过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性和谷胱甘肽（GSH）含量降低。同时，FB（40 μM）通过增加 ERK 和 p38 蛋白的磷酸化水平激活 ERK 和 p38 MAPK 信号通路。然而，SB202190、U0126 和二苯基碘氯化物（DPI）的预处理并不能改变 FB 触发的 ROS 产生和 HETs 形成，表明 FB 诱导的 HETs 是一种烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶、p38 和细胞外调节蛋白激酶（ERK）信号通路非依赖性过程。抑制肽基精氨酸脱亚氨酶 4（PAD4）酶和 P2×1 受体表明它们在 40 μM FB 触发的 HETs 中起着重要作用。本研究首次报道 40 μM FB 诱导嗜中性粒细胞释放 HETs，与 ROS 产生、PAD4 和 P2×1 有关，但与 NADPH 氧化酶、p38 和 ERK 信号通路无关，这可能为认识和理解 FB 在免疫毒性中的作用提供一个全新的视角。
