中性粒细胞胞外陷阱
炎症
活性氧
渗透(HVAC)
化学
肝损伤
DNA损伤
促炎细胞因子
体内
细胞生物学
生物物理学
DNA
免疫学
生物
生物化学
药理学
遗传学
材料科学
复合材料
作者
Qianru Chi,Tongwen Xu,Yujiao He,Zhe Li,Xinyu Tang,Xue Fan,Shu Li
标识
DOI:10.1016/j.jhazmat.2022.129502
摘要
The widespread use of plastics and the rapid development of nanotechnology bring convenience to our lives while also increasing the environmental burden and increasing the risk of exposure of organisms to nanoparticles (NPs). While recent studies have revealed an association between nanoparticles and liver injury, the intrinsic mechanism of NP exposure-induced liver damage remains to be explored. Here, we found that polystyrene nanoparticle (PSNP) exposure resulted in a significant increase in local neutrophil infiltration and neutrophil extracellular trap (NET) formation in the liver. Analysis of a coculture system of PBNs and AML12 cells revealed that PSNP-induced NET formation positively correlates with the reactive oxygen species (ROS)-NLRP3 axis. Inhibition of ROS and genetic and pharmacological inhibition of NLRP3 in AML12 can both alleviate PSNP-induced NET formation. In turn, exposure of mice to deoxyribonuclease I (DNase Ⅰ)-coated PSNPs disassembled NET in vivo, neutrophil infiltration in the liver was reduced, the ROS-NLRP3 axis was inhibited, and the expression of cytokines was markedly decreased. Collectively, our work reveals a mechanism of NET formation in PSNP exposure-induced liver inflammation and highlights the possible role of DNase Ⅰ as a key enzyme in degrading NET and alleviating liver inflammation.
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