Fig. 2
From: A promising frontier: targeting NETs for stroke treatment breakthroughs
Vital NETosis: Activation of PAD4 by Staphylococcus aureus and LPS occurs within 5-60 minutes after neutrophils are stimulated with the complement proteins TLR2, TLR4, and C3 and after the transfer of NE to the nucleus, which induces chromatin decondensation and subsequent destruction of the nuclear membrane. Notably, this process does not require the involvement of NADPH oxidase. Finally, protein-modified chromatin is expelled through vesicles, allowing neutrophils to survive and maintain their functionality. Mitochondrial NETosis: After neutrophils are stimulated by GM-CSF, LPS, and C5a, a subsequent increase in the Ca2+ concentration in mitochondria is induced by A23187, leading to the activation of the opening of the mPTP and the generation of mtROS. Following a process akin to suicidal NETosis, mitochondrial DNA releases NETs