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Untangling “NETosis” from NETs
Abstract
Neutrophil extracellular trap (NET) formation is a cellular function of neutrophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form NETs, neutrophils release a DNA scaffold consisting of mitochondrial DNA binding granule proteins. This process does not depend on cell death, but requires glycolytic ATP production for rearrangements in the microtubule network and F‐actin. Such cytoskeletal rearrangements are essential for both mitochondrial DNA release and degranulation. However, the formation of NETs has also been described as a distinct form of programed, necrotic cell death, a process designated “NETosis.” Necrotic cell death of neutrophils is associated with the permeabilization of both plasma and nuclear membranes resulting in a kind of extracellular cloud of nuclear DNA. The molecular mechanisms eliciting necrotic neutrophil death have been investigated and appear to be different from those responsible for NET formation following mitochondrial DNA release. Here, we discriminate between the mechanisms responsible for the release of mitochondrial versus nuclear DNA and address their respective functions. Our aim is to clarify existing differences of opinion in the fields of NET formation and neutrophil death.
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“activated neutrophils rapidly form extracellular traps (NETs), which are web-like structures with enriched granule proteins assembled on a mitochondrial DNA (mtDNA) scaffold [30–36].”
From Nascent RHOH acts as a molecular brake on actomyosin-mediated effector functions of inflammatory neutrophils (2022) · cites this paper as [34]
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Borges, L., Pithon-Curi, T. C., Curi, R., & Hatanaka, E. (2020) · Mediators of Inflammation · doi:10.1155/2020/8829674 · Cited by 235
The role of the host—Neutrophil biology
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Peng, S., Stojkov, D., Gao, J., Oberson, K., Latzin, P., Casaulta, C., Yousefi, S., & Simon, H.-U. (2022) · PLOS Biology · doi:10.1371/journal.pbio.3001794 · Cited by 15
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Metadata
- Authors
- Yousefi, S., Stojkov, D., Germic, N., Simon, D., Wang, X., Benarafa, C., & Simon, H.
- Affiliations
- Institute of Pharmacology University of Bern Bern Switzerland
- Department of Dermatology, Inselspital Bern University Hospital, University of Bern Bern Switzerland
- Institute of Virology and Immunology Mittelhäusern Switzerland
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2019-01-15
- Volume
- 49
- Issue
- 2
- Pages
- 221-227
- ISSN
- 0014-2980
- 1521-4141
- Cited by
- 162
- References
- 18
- Language
- en
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_173215, 310030_166473)
- Horizon 2020 (642295)
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- Yousefi, S., Stojkov, D., Germic, N., Simon, D., Wang, X., Benarafa, C., & Simon, H. (2019). Untangling “NETosis” from NETs. European Journal of Immunology. https://doi.org/10.1002/eji.201747053
