Fig. 1
From: The role of neutrophil extracellular traps in cancer progression, metastasis and therapy
NADPH oxidase (NOX)-dependent NET formation pathways. Neutrophils are activated by extracellular microbes or PMA, LPS and IL-8, followed by activation of various pathways, including MEK/Erk, c-JNK, and PI3K/Akt signals. The endoplasmic calcium in the cytoplasm then phosphorylates NADPH Oxidase (Nox2), thereby driving the production of reactive oxygen species (ROS). Subsequently, neutrophil elastase (NE) and myeloperoxidase (MPO) stored in cytoplasmic granules translocate into the nucleus and contribute to chromatin decondensation with the assistance of calcium-dependent protein protein-arginine deiminase type 4 (PAD4), which citrullinates histones. Decondensed chromatin mixed with granule proteins is first released into the cytoplasm and then out of the cell membrane, and forms Neutrophil Extracellular Traps (NETs).