The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps
Abstract
Neutrophil extracellular traps (NETs) represent extracellular structures able to bind and kill microorganisms. It is believed that they are generated by neutrophils undergoing cell death, allowing these dying or dead cells to kill microbes. We show that, following priming with granulocyte/macrophage colony-stimulating factor (GM-CSF) and subsequent short-term toll-like receptor 4 (TLR4) or complement factor 5a (C5a) receptor stimulation, viable neutrophils are able to generate NETs. Strikingly, NETs formed by living cells contain mitochondrial, but no nuclear, DNA. Pharmacological or genetic approaches to block reactive oxygen species (ROS) production suggested that NET formation is ROS dependent. Moreover, neutrophil populations stimulated with GM-CSF and C5a showed increased survival compared with resting neutrophils, which did not generate NETs. In conclusion, mitochondrial DNA release by neutrophils and NET formation do not require neutrophil death and do also not limit the lifespan of these cells.
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In the citing paper
“Different cellular lineages (10–18) may extrude their mitochondria upon activation.”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [10]
In the citing paper
“Various cellular lineages are capable of extruding their mitochondria. Activated mast cells10, T-cells11, eosinophils12, hepatocytes13, neutrophils14–16 and platelets17,18, in addition to damaged organs or tissues7,13,19,20, release extracellular mitochondria.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [14]
In the citing paper
“during immune response, neutrophils utilize mtDNA as a structural molecule to bind cytotoxic proteins into neutrophil extracellular traps (NETs), which are then released onto advancing plaque biofilms (Yousefi et al., 2009)”
From Successful enrichment and recovery of whole mitochondrial genomes from ancient human dental calculus (2016) · cites this paper as Yousefi et al., 2009
In the citing paper
“Several reports demonstrate that a considerable fraction of the nucleic acids contained in NETs is of mitochondrial, rather than nuclear, origin [724–728].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [724]
In the citing paper
“both NETotic cell death and NET extrusion in the absence of RCD appears to rely on the activity of NADPH oxidases [724, 736, 737].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [724]
In the citing paper
“NET extrusion per se does not necessarily result in cellular lysis [722, 724, 735].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [724]
Citations
Cites
Neutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268
Novel cell death program leads to neutrophil extracellular traps
Fuchs, T. A., Abed, U., Goosmann, C., Hurwitz, R., Schulze, I., Wahn, V., Weinrauch, Y., Brinkmann, V., & Zychlinsky, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200606027 · Cited by 3,197
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood
Clark, S. R., Ma, A. C., Tavener, S. A., McDonald, B., Goodarzi, Z., Kelly, M. M., Patel, K. D., Chakrabarti, S., McAvoy, E., Sinclair, G. D., et al. (2007) · Nature Medicine · doi:10.1038/nm1565 · Cited by 2,309
Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis
Yousefi, S., Perozzo, R., Schmid, I., Ziemiecki, A., Schaffner, T., Scapozza, L., Brunner, T., & Simon, H.-U. (2006) · Nature Cell Biology · doi:10.1038/ncb1482 · Cited by 1,158
Self-citationCatapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense
Yousefi, S., Gold, J. A., Andina, N., Lee, J. J., Kelly, A. M., Kozlowski, E., Schmid, I., Straumann, A., Reichenbach, J., Gleich, G. J., et al. (2008) · Nature Medicine · doi:10.1038/nm.1855 · Cited by 967
Self-citationBeneficial suicide: why neutrophils die to make NETs
Brinkmann, V., & Zychlinsky, A. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1710 · Cited by 937
Selective fluorescent imaging of superoxide in vivo using ethidium-based probes
Robinson, K. M., Janes, M. S., Pehar, M., Monette, J. S., Ross, M. F., Hagen, T. M., Murphy, M. P., & Beckman, J. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601945103 · Cited by 777
von Köckritz‐Blickwede, M., Goldmann, O., Thulin, P., Heinemann, K., Norrby‐Teglund, A., Rohde, M., & Medina, E. (2008) · Blood · doi:10.1182/blood-2007-07-104018 · Cited by 566
Gupta, A. K., Hasler, P., Holzgreve, W., Gebhardt, G., & Hahn, S. (2005) · Human Immunology · doi:10.1016/j.humimm.2005.11.003 · Cited by 412
Neutrophil apoptosis pathways and their modifications in inflammation
Simon, H. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00038.x · Cited by 350
Self-citationMartinelli, S., Urosevic, M., Daryadel, A., Oberholzer, P. A., Baumann, C. K., Fey, M. F., Dummer, R., Simon, H., & Yousefi, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405883200 · Cited by 294
Self-citationConus, S., Perozzo, R., Reinheckel, T., Peters, C., Scapozza, L., Yousefi, S., & Simon, H. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072152 · Cited by 277
Self-citationvon Gunten, S., Yousefi, S., Seitz, M., Jakob, S. M., Schaffner, T. J., Seger, R. A., Takala, J. A., Villiger, P. M., & Simon, H. (2005) · Blood · doi:10.1182/blood-2004-10-4112 · Cited by 217
Self-citationvon Gunten, S., Schaub, A., Vogel, M., Stadler, B. M., Miescher, S., & Simon, H. (2006) · Blood · doi:10.1182/blood-2006-05-021568 · Cited by 135
Self-citationNeutrophil apoptosis mediated by nicotinic acid receptors (GPR109A)
Kostylina, G., Simon, D., Fey, M. F., Yousefi, S., & Simon, H. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402238 · Cited by 119
Self-citationFungal and Bacterial Killing by Neutrophils
Ermert, D., Zychlinsky, A., & Urban, C. F. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-204-5_21 · Cited by 83
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Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
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Extracellular DNA traps promote thrombosis
Fuchs, T. A., Brill, A. G., Duerschmied, D., Schatzberg, D., Monestier, M., Myers, D. D., Wrobleski, S. K., Wakefield, T. W., Hartwig, J. H., & Wagner, D. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005743107 · Cited by 2,591
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Self-citationNeutrophils, from Marrow to Microbes
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Metadata
- Authors
- Yousefi, S., Mihalache, C., Kozlowski, E., Schmid, I., & Simon, H. U.
- Affiliations
- University of Bern (CH)
- Corresponding author
- Yousefi, S
- ORCID
- Venue
- Cell Death & Differentiation
- Published
- 2009-07-17
- Volume
- 16
- Issue
- 11
- Pages
- 1438-1444
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W2056112680
- Cited by
- 1,036
- References
- 17
- Citations by year
- 2026: 84 · 2025: 82 · 2024: 67 · 2023: 89 · 2022: 92 · 2021: 93 · 2020: 84 · 2019: 79 · 2018: 66 · 2017: 57 · 2016: 66 · 2015: 43 · 2014: 28 · 2013: 36 · 2012: 36
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (107526, 112078)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- neutrophil extracellular traps, mitochondrial DNA release, neutrophil survival, reactive oxygen species, GM-CSF, TLR4, C5a receptor, innate immunity, antimicrobial defense
- MeSH terms
- DNA, Mitochondrial, Humans, Neutrophils, Complement C5a, Granulocyte-Macrophage Colony-Stimulating Factor, Apoptosis, Reactive Oxygen Species, Neutrophil Activation, Toll-Like Receptor 4
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