CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses
CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses
复制标题
DOI：
10.1007/s00204-022-03357-4
复制
发表时间：
2022-08
影响因子：
6.1
通讯作者：
Liqiang Jiang;W. Liu;Jingnan Xu;Xinxin Gao;Haiguang Zhao;Shurou Li;Wenlong Huang;Zhengtao Yang;Zhengkai Wei
中科院分区：
文献类型：
--
作者：
Liqiang Jiang;W. Liu;Jingnan Xu;Xinxin Gao;Haiguang Zhao;Shurou Li;Wenlong Huang;Zhengtao Yang;Zhengkai Wei
随着纳米氧化铜(CuO-NPs)的广泛使用，其对环境和生物健康的潜在毒性已引起人们的密切关注。异嗜性细胞外陷阱(HETs)是鸡嗜异体细胞抵抗不利刺激的一种先天免疫机制，但过量的HETs会造成损害。在此，我们探讨了CuO-NPs在体外对HETs形成的影响及其机制，并进一步评价了HETs在鸡肝肾损伤中的潜在作用。结果表明，CuO-NPs可诱导典型的HETs的形成，这种形成依赖于NADPH氧化酶、P38和细胞外调节蛋白激酶(ERK1/2)途径以及糖酵解。体内实验中，荧光微孔板和形态分析表明，CuO-NPs可升高鸡血清中HETs的水平，并引起肝、肾损伤。同时，CuO-NPs引起肝脏氧化应激(丙二醛、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶失衡)，并诱导其炎症和凋亡相关因子(IL-1、IL-6、肿瘤坏死因子-β、环氧合酶-2、诱导型一氧化氮合酶、NLRP3和半胱氨酸天冬氨酸氨基转移酶-1、3、11)表达增加。然而，这些结果被DNase I(HETs降解剂)显著改变。综上所述，本研究首次证明了CuO-NPs可诱导HETs的形成，HETs通过促进氧化应激和炎症反应而加重鸡肝肾的病理损伤，为研究CuO-NPs过度暴露引起的免疫毒性和潜在的防治靶点提供了新的见解。
With the widespread use of copper oxide nanoparticles (CuO-NPs), their potential toxicity to the environment and biological health has attracted close attention. Heterophil extracellular traps (HETs) are an innate immune mechanism of chicken heterophils against adverse stimuli, but excessive HETs cause damage. Here, we explored the effect and mechanism of CuO-NPs on HETs formation in vitro and further evaluated the potential role of HETs in chicken liver and kidney injury. Heterophils were exposed to 5, 10, and 20 µg/mL of CuO-NPs for 2 h. The results showed that CuO-NPs induced typical HETs formation, which was dependent on NADPH oxidase, P38 and extracellular regulated protein kinases (ERK1/2) pathways, and glycolysis. In in vivo experiments, fluorescence microplate and morphological analysis showed that CuO-NPs elevated the level of HETs in chicken serum and caused liver and kidney damage. Meanwhile, CuO-NPs caused hepatic oxidative stress (MDA, SOD, CAT, and GSH–PX imbalance), and also induced an increase in mRNA expression of their inflammatory and apoptosis-related factors (IL-1β, IL-6, TNF-α, COX-2, iNOS, NLRP3, and Caspase-1, 3, 11). However, these results were significantly altered by DNase I (HETs degradation reagent). In conclusion, the present study demonstrates for the first time that CuO-NPs induce the formation of HETs and that HETs exacerbate pathological damage in chicken liver and kidney by promoting oxidative stress and inflammation, providing insights into immunotoxicity and potential prevention and treatment targets caused by CuO-NPs overexposure.