Figure 1.

(I) Several stimuli (e.g., bacteria, viruses, fungi) initiate NETosis by binding to neutrophil receptors (e.g., Fc receptors, TLRs), which activate the endoplasmic reticulum to release stored calcium ions. (II) Elevated cytoplasmic calcium levels increase PKC activity, which induces NADPH oxidase to assemble into a functional complex (PHOX). (II-a) Subsequently, PHOX (or alternatively the mitochondrial respiratory chain) generate ROS. (III) ROS generation leads to the rupture of granules and the nuclear envelope. (III-a) Meanwhile, NE and MPO translocate to the nucleus. (III-b) As a result, histone deamination and chromatin de-condensation contribute to the formation of NETs. (IV) Finally, the rupture of the plasma membrane causes neutrophil lysis and allows the release of NETs.