中性粒细胞胞外陷阱
自噬
PI3K/AKT/mTOR通路
蛋白激酶B
化学
细胞生物学
激酶
免疫系统
佛波
脂多糖
细胞外
先天免疫系统
蛋白激酶A
MAPK/ERK通路
信号转导
免疫学
蛋白激酶C
生物
炎症
细胞凋亡
生物化学
作者
Shuzi Ye,Yu Ma,Siwen Li,Sijia Luo,Lai Wei,Die Hu,Fang Xiao
标识
DOI:10.1016/j.jhazmat.2023.131755
摘要
NO2 has been known to impair immunity and exacerbate susceptibility to infectious diseases. However, scant notice has been taken of the effect of NO2 on neutrophils. Neutrophil extracellular traps (NETs) formation is necessary for NETosis development by neutrophils as an immune system against pathogens. By analyzing the morphology and signature components of NETs, we focused for the first time on finding that 10 ppm of NO2 exposure for 15 consecutive days can hinder the formation of NETs. Next, we used NO2 in vivo derivatives to probe the mechanism for NETs formation in vitro. Our findings showed that NO2 suppression of respiratory burst levels and mitogen-activated protein kinase (MAPK)/Phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling was related to NO2 reduction in NETs formation. Inhibition of phorbol myristate acetate (PMA)-induced NETs formation by NO2 hindered autophagy, as evidenced by increased mTOR protein expression, decreased LC3 protein expression, and reduced autophagic vesicles. By activating mTOR-mediated autophagy, rapamycin (Rapa) reduced the inhibition of PMA-induced NETs by NO2. This study will provide valuable insights into the mechanisms of immunotoxicity of NO2, new insights into the etiology of diseases linked to NETs formation, and a theoretical basis for protection against such illnesses.
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