Bongkrekic acid induced neutrophil extracellular traps via p38, ERK, PAD4, and P2X1-mediated signaling

• Published in: Toxicology and applied pharmacology Vol. 423; p. 115580
• Main Authors: Zhou, Ershun, Sun, Youpeng, Fu, Yiwu, Wang, Xia, Zhu, Xingyi, Wu, Zhikai, Li, Peixuan, Wang, Jingjing, Yang, Zhengtao
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.07.2021
• Subjects: Bongkrekic acid; Immunotoxicity; Neutrophil extracellular traps; Signaling pathway; Bongkrekic acid; Signaling pathway; Neutrophil extracellular traps; Immunotoxicity
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2021.115580

Bongkrekic acid (BKA) produced by pseudomonas cocovenenans is a deadly toxin, and is mainly found in spoiled or fermented foods. However, less is known on its immunotoxicity. Neutrophil extracellular traps (NETs) are a novel effector mechanism of neutrophils against invading pathogens, but excessive NETs also contribute to tissue damage. This study aimed to investigate NET formation triggered by BKA in murine neutrophils, and describe its characteristics and potential mechanisms. Our results showed that BKA triggered NET formation via co-localization of DNA and histone or MPO by immunostaining. Moreover, BKA-triggered NET formation was dose- and time-dependent via NET quantification based on Picogreen-derived fluorescence intensities. Furthermore, BKA increased ROS production in neutrophils. Pharmacological inhibition indicated that BKA-triggered NET formation was associated with ROS-p38 and –ERK signaling pathways, but independent on NADPH oxidase. Besides, PAD4 and P2X1 receptor also mediated BKA-triggered NET formation. To our knowledge, all these findings provide for the first time an initial understanding of BKA on innate immunity, which might be helpful for further investigation on BKA immunotoxicity. •BKA exposure triggered NET formation.•BKA-triggered NET formation was concentration- and time-dependent.•BKA exposure increased ROS production in neutrophils.•BKA-triggered NET formation was associated with p38 and ERK signaling pathways•BKA-triggered NET formation was mediated by PAD4 and P2X1 receptor.