Neutrophil extracellular traps (NETs): Double-edged swords of innate immunity

By M. Kaplan, M. Radic. Journal of Immunology, 2012

1,118 citations recorded by the source corpus.

Spectacular images of neutrophils ejecting nuclear chromatin and bactericidal proteins, in response to microbes, were first reported in 2004. As externalized chromatin could entangle bacteria, these structures were named neutrophil extracellular traps (NETs). Subsequent studies identified microorganisms and sterile conditions that stimulate NETs, as well as additional cell types that release extracellular chromatin. The release of NETs is the most dramatic stage in a cell death process called NETosis. Experimental evidence suggests that NETs participate in pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. Exaggerated NETosis or diminished NET clearance likely increases risk of autoreactivity to NET components. The biological significance of NETs is just beginning to be explored. A more complete integration of NETosis within immunology and pathophysiology will require better understanding of NET properties associated with specific disease states and microbial infections. This may lead to the identification of important therapeutic targets.

Subfields: Immunology, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c8f098bfa8842aa20bf7a5855bac560f19eab86a

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In Immunology

1. V. Brinkmann
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In Immunology and Allergy

1. Arturo Zychlinsky

In Molecular Biology

1. V. Brinkmann
2. Arturo Zychlinsky

Citations in the corpus

• Gasdermin D plays a vital role in the generation of neutrophil extracellular traps (2018, background): “NETs are a double­edged sword; they are bene­ ficial in infections but pathogenic by exposing autoantigens and promoting thrombosis (14).”
• SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx (2015, background): “Previous studies suggest the existence of NOX-independent NETosis, as demonstrated by the inability of DPI to suppress NET release (30, 31).”
• Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment (2020, background): “NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils that bind and kill extracellular pathogens while minimizing damage to the host cells [30].”
• Diverse stimuli engage different neutrophil extracellular trap pathways (2017, background): “DOI: 10.7554/eLife.24437 1 of 21 activate protein kinase C (PKC), which in turn leads to calcium fluxes within the cell and activation of the NADPH oxidase signalling cascade resulting in the production of reactive oxygen species (ROS) (Hakkim et al., 2011; Kaplan and Radic, 2012).”