ROS induces NETosis by oxidizing DNA and initiating DNA repair

Reactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. This paper investigates how ROS induces NETosis. The study shows that NADPH oxidase-dependent NETosis leads to DNA damage, followed by the translocation of proliferating cell nuclear antigen (PCNA) into the nucleus. Inhibition of the DNA repair complex assembly (involving APE1, PARP, and DNA ligase) suppresses NETosis, while later repair steps do not. Excess ROS oxidizes DNA (e.g., guanine to 8-oxoguanine), and subsequent DNA repair leads to chromatin decondensation and NETosis.

Dhia Azzouz, Meraj A. Khan, Nades Palaniyar