1. Figure 1 Mechanisms of neutrophil extracellular trap formation
Figure 1 | Mechanisms of neutrophil extracellular trap formation. a | Classic late lytic neutrophil extracellular trap (NET) formation is induced by the recognition of stimuli, such as phorbol myristate acetate (PMA), antibodies or cholesterol crystals, with a duration of 2–4 h. In conjunction with NADPH activation through the protein kinase C (PKC) or RAF–MEK–MAPK pathways, reactive oxygen species (ROS) are produced and protein-arginine deaminase type 4 (PAD4) is activated, which enables citrullination of histones and subsequent chromatin decondensation. Signal inhibitory receptor on leukocytes 1 (SIRL1) is involved in a NET-specific signalling pathway, and inhibition of SIRL1 can prevent NET formation in response to autoantibodies and bacteria without affecting oxidant production, but details of the downstream signalling pathway in NET formation are currently unknown. Translocation of myeloperoxidase (MPO) and neutrophil elastase (NE) into the nucleus leads to further unfolding of chromatin, and thereafter, the nuclear membrane is disrupted. Released chromatin is decorated with granular and cytosolic proteins, and finally, NETs are released. Neutrophils lose their viability after NET formation. b | Early non-lytic NET formation is induced within 5–60 min by the recognition of stimuli through Toll-like receptor 2 (TLR2), TLR4 or complement receptors independent of NAPDH oxidase activation. The interaction between an unknown ligand on platelets and lymphocyte function-associated antigen 1 (LFA1) on neutrophils plays a pivotal part in some situations. With Staphylococcus aureus stimulation, platelets might not be required for non-lytic NET formation. Along with PAD4 activation, chromatin decondensation proceeds and protein-decorated chromatin is expelled via vesicles without plasma membrane disruption. After the release of NETs, neutrophils are still alive and possess the ability to phagocytose and chemotax. DAMPs, damage-associated molecular patterns; E. coli, Escherichia coli; Fc, antibody crystallizable fragment.
Honda, M. & Kubes, P. (2018) Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system
Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro