Fig. 1. The formation of neutrophil extracellular traps (Created with Biorender.com).

After being stimulated by external factors, neutrophils activate NADPH to release ROS. The activation of NADPH and ROS leads to the secretion of PAD4, which acts on eosinophilic granules and induces the release of proteins such as NE and MPO. These granular proteins will cause chromatin decondensation, and the secreted PAD4 will lead to histone citrullination. After the neutrophil plasma membrane ruptures, the decondensed chromatin combines with the granular proteins and is released to form a network-like DNA structure extracellularly. GSDMD is involved in the formation of eosinophilic granules and membrane pores. There are two types of neutrophils that can produce NETs, PMNs and LDGs. The production of NETs by neutrophils is involved in the occurrence of various skin diseases, such as pyoderma gangrenosum, PAPA syndrome, Behcet’s syndrome, pyogenic hidradenitis, adult Still’s disease, subcorneal pustular dermatosis, and Schnitzler’s syndrome. NADPH: nicotinamide adenine dinucleotide phosphate, ROS: reactive oxygen species, PAD: peptidylarginine deiminase, NE: neutrophil elastase, MPO: myeloperoxidase, DNA: deoxyribonucleic acid, PMNs: polymorphonuclear neutrophils, LDGs: low-density granulocytes, NETs: neutrophil extracellular traps, GSDMD: gasdermin D.