自噬
活性氧
细胞生物学
p38丝裂原活化蛋白激酶
中性粒细胞胞外陷阱
MAPK/ERK通路
呼吸爆发
激酶
细胞外
程序性细胞死亡
化学
信号转导
生物
生物化学
炎症
免疫学
细胞凋亡
作者
Siwen Li,Yu Ma,Shuzi Ye,Die Hu,Fang Xiao
标识
DOI:10.1016/j.jhazmat.2021.126758
摘要
Organophosphorus compounds were proposed to impair immune surveillance and increase the total burden of pathogens. However, scarce attention has been paid to the effects of organophosphate flame retardants (OPFRs) on neutrophils. Previous literature outlined that neutrophil extracellular traps (NETs) death (NETosis) is associated with autophagy-related signaling. Here we found that 20 μM diphenyl phosphate (DPHP) could promote NETs formation via assessing markers of NETs and the morphological changes. Concurrently, flow cytometry and western blot analysis revealed that DPHP-triggered NETs formation was associated with reactive oxygen species (ROS) burst and activation of extracellular signal-regulated kinase (ERK) and p38. Additionally, the results revealed that autophagy occurred in DPHP-triggered NETs formation, manifested as enhanced LC3B protein expressions and reduced p62 protein expressions. Mechanism dissection revealed that inhibition of autophagy by 3-methyladenine (3-MA) alleviated the ROS burst and subsequent NETosis caused by DPHP. Conversely, autophagy enhancer Rapamycin (Rapa) augmented the above effects of DPHP, including the generation of ROS and NETosis. Collectively, these data suggested ERK/p38 signaling and ROS burst might be an important cause of DPHP-triggered NETs formation, while suppression of excessive autophagy could rescue these actions. These observations provided a theoretical basis for the treatment and prevention of OPFRs-induced immunotoxicity.
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