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Abstract
Neutrophils are the major antimicrobial cells of the innate immune system, which are recruited rapidly to the sites of infection and provide the primary defense against pathogens. Recent evidence suggests that neutrophils undergo a distinct cell death mechanism called NETosis, which not only contributes to the host defense, but also leads to severe pathological immune responses in cases of dysregulation. Here, we review the general features of NETosis as well as the generation of autoantigens and damage-associated molecular patterns by NETosis in autoimmune diseases. This review discusses the pathogenic role of NETosis in rheumatoid arthritis and systemic lupus erythematosus, where neutrophils may play a key role in the pathogenesis of these diseases, and suggest the possibility of neutrophil extracellular traps as biomarkers and therapeutic targets for the treatment of autoimmune diseases.
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Figure 1.
NETosis. NETosis is initiated by binding of ligands such as immune complexes and microbes to their receptors on neutrophils, followed by calcium influx and reactive oxygen species (ROS) production. The intracellular signaling induces histone citrullination, chromatin decondensation, and disintegration of nuclear and granular membranes, which enables granular proteins to translocate to the nucleus. Subsequently, granular and cytoplasmic proteins are mixed with the chromatin. Finally, the neutrophil membrane ruptures and fully functional web-like neutrophil extracellular traps (NETs) are released.
Table 1.
Neutrophil extracellular trap-associated proteins [7-10]
Table 2.
NETosis inducers [3,12,13]
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