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Novel cell death program leads to neutrophil extracellular traps
Tobias A. Fuchs1,5,
Ulrike Abed1,2,
Christian Goosmann1,2,
Robert Hurwitz3,
Ilka Schulze4,
Volker Wahn4,
Yvette Weinrauch5,
Volker Brinkmann2, , and
Arturo Zychlinsky1
1 Department for Cellular Microbiology, 2 Microscopy Core Facility, and 3 Protein Purification Core Facility, Max-Planck Institute for Infection Biology, 10117 Berlin, Germany 4 Department for Paediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany 5 Department of Microbiology, New York University School of Medicine, New York, NY 10016
Correspondence to Arturo Zychlinsky: zychlinsky{at}mpiib-berlin.mpg.de
Abstract:
Neutrophil extracellular traps (NETs) are extracellular structurescomposed of chromatin and granule proteins that bind and killmicroorganisms. We show that upon stimulation, the nuclei ofneutrophils lose their shape, and the eu- and heterochromatinhomogenize. Later, the nuclear envelope and the granule membranesdisintegrate, allowing the mixing of NET components. Finally,the NETs are released as the cell membrane breaks. This celldeath process is distinct from apoptosis and necrosis and dependson the generation of reactive oxygen species (ROS) by NADPHoxidase. Patients with chronic granulomatous disease carry mutationsin NADPH oxidase and cannot activate this cell-death pathwayor make NETs. This novel ROS-dependent death allows neutrophilsto fulfill their antimicrobial function, even beyond their lifespan.
V. Brinkmann and A. Zychlinsky contributed equally to this paper.
Abbreviations used in this paper: AT, 3-amino-1,2,4-triazole;CGD, chronic granulomatous disease; DPI, diphenylene iodonium;GO, glucose oxidase; IL, interleukin; LPS, lipopolysaccharide;MNase, micrococcal nuclease; MOI, multiplicity of infection;NETs, neutrophil extracellular traps; PBMC, peripheral bloodmononuclear cells; PS, phosphatidylserine; ROS, reactive oxygenspecies.
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Novel territory for neutrophils in the pathogenesis of ANCA-associated vasculitides.
M. Chen and C. G. M. Kallenberg (2009)
Nephrol. Dial. Transplant.
24, 3618-3620
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Delayed but functional neutrophil extracellular trap formation in neonates.
V. Marcos, C. Nussbaum, L. Vitkov, A. Hector, E.-M. Wiedenbauer, D. Roos, T. Kuijpers, W. D. Krautgartner, O. Genzel-Boroviczeny, M. Sperandio, et al. (2009)
Blood
114, 4908-4911
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Neutrophil antimicrobial defense against Staphylococcus aureus is mediated by phagolysosomal but not extracellular trap-associated cathelicidin.
N. J. Jann, M. Schmaler, S. A. Kristian, K. A. Radek, R. L. Gallo, V. Nizet, A. Peschel, and R. Landmann (2009)
J. Leukoc. Biol.
86, 1159-1169
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Shed Syndecan-1 Restricts Neutrophil Elastase from {alpha}1-Antitrypsin in Neutrophilic Airway Inflammation.
S. C. H. Chan, V. O. Y. Leung, M. S. M. Ip, and D. K. Y. Shum (2009) 41, 620-628
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Reconstitution of protection against Aspergillus infection in chronic granulomatous disease (CGD).
Q. Remijsen, P. Vandenabeele, J. Willems, and T. W. Kuijpers (2009)
Blood
114, 3497
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Virulence and Cellular Interactions of Burkholderia multivorans in Chronic Granulomatous Disease.
A. M. Zelazny, L. Ding, H. Z. Elloumi, L. R. Brinster, F. Benedetti, M. Czapiga, R. L. Ulrich, S. J. Ballentine, J. B. Goldberg, E. P. Sampaio, et al. (2009)
Infect. Immun.
77, 4337-4344
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Restoration of NET formation by gene therapy in CGD controls aspergillosis.
M. Bianchi, A. Hakkim, V. Brinkmann, U. Siler, R. A. Seger, A. Zychlinsky, and J. Reichenbach (2009)
Blood
114, 2619-2622
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Contributions to Neutropenia from PFAAP5 (N4BP2L2), a Novel Protein Mediating Transcriptional Repressor Cooperation between Gfi1 and Neutrophil Elastase.
S. J. Salipante, M. E. B. Rojas, B. Korkmaz, Z. Duan, J. Wechsler, K. F. Benson, R. E. Person, H. L. Grimes, and M. S. Horwitz (2009)
Mol. Cell. Biol.
29, 4394-4405
|Abstract »|Full Text »|PDF »
LAMPs and NETs in the Pathogenesis of ANCA Vasculitis.
X. Bosch (2009)
J. Am. Soc. Nephrol.
20, 1654-1656
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Catalytic Activity and Inhibition of Wegener Antigen Proteinase 3 on the Cell Surface of Human Polymorphonuclear Neutrophils.
B. Korkmaz, J. Jaillet, M.-L. Jourdan, A. Gauthier, F. Gauthier, and S. Attucci (2009)
J. Biol. Chem.
284, 19896-19902
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Cellular expression and antimicrobial function of a phylogenetically conserved novel histone 1x-like protein on mouse cells: a potential new class of pattern recognition receptor.
D. L. Evans, M. A. Connor, L. D. Moss, S. Lackay, J. H. Leary III, T. Krunkosky, and L. Jaso-Friedmann (2009)
J. Leukoc. Biol.
86, 133-141
|Abstract »|Full Text »|PDF »
