DEHP induces neutrophil extracellular traps formation and apoptosis in carp isolated from carp blood via promotion of ROS burst and autophagy

• Published in: Environmental pollution (1987) Vol. 262; p. 114295
• Main Authors: Yirong, Cao, Shengchen, Wang, Jiaxin, Sun, Shuting, Wang, Ziwei, Zhang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2020
• Subjects: Apoptosis; Autophagy; carp; Di (2-ethylhexyl) phthalate; DNA; dynein ATPase; endocrine-disrupting chemicals; humans; immunotoxicity; Neutrophil extracellular traps; neutrophils; phthalates; quantitative analysis; reactive oxygen species; ROS production; Di (2-ethylhexyl) phthalate; Autophagy; Neutrophil extracellular traps; ROS production; Apoptosis
• ISSN: 0269-7491; 1873-6424; 1873-6424
• DOI: 10.1016/j.envpol.2020.114295

Di (2-ethylhexyl) phthalate (DEHP), a widely spreading environmental endocrine disruptor, has been confirmed to adversely affect the development of animals and humans. The formation of neutrophil extracellular traps (NETs) termed NETosis, is a recently identified antimicrobial mechanism for neutrophils. Though previous researches have investigated inescapable role of the immunotoxicity in DEHP-exposed model, relatively little is known about the effect of DEHP on NETs. In this study, carp peripheral blood neutrophils were treated with 40 and 200 μmol/L DEHP to investigate the underlying mechanisms of DEHP-induced NETs formation. Through the morphological observation of NETs and quantitative analysis of extracellular DNA, we found that DEHP exposure induced NETs formation. Moreover, our results proved that DEHP could increase reactive oxygen species (ROS) levels, decrease the expression of the anti-autophagy factor (mTOR) and the anti-apoptosis gene Bcl-2, and increase the expression of pro-autophagy genes (Dynein, Beclin-1 and LC3B) and the pro-apoptosis factors (BAX, Fas, FasL, Caspase3, Caspase8, and Caspase9), thus promoting autophagy and apoptosis. These results indicate that DEHP-induced ROS burst stimulates NETs formation mediated by autophagy and increases apoptosis in carp neutrophils. [Display omitted] •DEHP induces neutrophil extracellular traps formation in carp.•DEHP causes carp neutrophil apoptosis via mitochondrial and death receptor pathways.•DEHP induces ROS production.•DEHP exposure promotes carp neutrophil autophagy. The formation of neutrophil extracellular traps (NETs) is a newly identified antimicrobial mechanism for neutrophils. However, relatively little is known about the effect of DEHP on NETs.