Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Volker Brinkmann,1Ulrike Reichard,1,2Christian Goosmann,1,2Beatrix Fauler,1Yvonne Uhlemann,2David S. Weiss,2Yvette Weinrauch,3Arturo Zychlinsky2*
Neutrophils engulf and kill bacteria when their antimicrobialgranules fuse with the phagosome. Here, we describe that, uponactivation, neutrophils release granule proteins and chromatinthat together form extracellular fibers that bind Gram-positiveand -negative bacteria. These neutrophil extracellular traps(NETs) degrade virulence factors and kill bacteria. NETs areabundant in vivo in experimental dysentery and spontaneous humanappendicitis, two examples of acute inflammation. NETs appearto be a form of innate response that binds microorganisms, preventsthem from spreading, and ensures a high local concentrationof antimicrobial agents to degrade virulence factors and killbacteria.
1 Microscopy Core Facility, Max Planck Institute for Infection Biology, Schumannstrasse 21/22, 10117 Berlin, Germany. 2 Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Schumannstrasse 21/22, 10117 Berlin, Germany. 3 Department of Microbiology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
* To whom correspondence should be addressed. E-mail: zychlinsky{at}mpiib-berlin.mpg.de
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)
Am. J. Respir. Cell Mol. Biol.
41, 620-628
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
Cell-Free DNA as a Noninvasive Acute Rejection Marker in Renal Transplantation.
V. Garcia Moreira, B. Prieto Garcia, J. M. Baltar Martin, F. Ortega Suarez, and F. V. Alvarez (2009)
Clin. Chem.
55, 1958-1966
|Abstract »|Full Text »|PDF »
Extracellular DNA Is Required for Root Tip Resistance to Fungal Infection.
F. Wen, G. J. White, H. D. VanEtten, Z. Xiong, and M. C. Hawes (2009)
Plant Physiology
151, 820-829
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
Coagulation and innate immune responses: can we view them separately?.
Novel territory for neutrophils in the pathogenesis of ANCA-associated vasculitides.
M. Chen and C. G. M. Kallenberg (2009)
Nephrol. Dial. Transplant.
|Full Text »|PDF »
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 »
Human Neutrophils Kill Streptococcus pneumoniae via Serine Proteases.
Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5.
A. F. Carlin, Y.-C. Chang, T. Areschoug, G. Lindahl, N. Hurtado-Ziola, C. C. King, A. Varki, and V. Nizet (2009)
J. Exp. Med.
206, 1691-1699
|Abstract »|Full Text »|PDF »
LAMPs and NETs in the Pathogenesis of ANCA Vasculitis.
X. Bosch (2009)
J. Am. Soc. Nephrol.
20, 1654-1656
|Full Text »|PDF »
Peroxidasin Is Secreted and Incorporated into the Extracellular Matrix of Myofibroblasts and Fibrotic Kidney.
Z. Peterfi, A. Donko, A. Orient, A. Sum, A. Prokai, B. Molnar, Z. Vereb, E. Rajnavolgyi, K. J. Kovacs, V. Muller, et al. (2009)
Am. J. Pathol.
175, 725-735
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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 »
Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates.
C. C. Yost, M. J. Cody, E. S. Harris, N. L. Thornton, A. M. McInturff, M. L. Martinez, N. B. Chandler, C. K. Rodesch, K. H. Albertine, C. A. Petti, et al. (2009)
Blood
113, 6419-6427
|Abstract »|Full Text »|PDF »
Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps.
A. B. Guimaraes-Costa, M. T. C. Nascimento, G. S. Froment, R. P. P. Soares, F. N. Morgado, F. Conceicao-Silva, and E. M. Saraiva (2009)
PNAS
106, 6748-6753
|Abstract »|Full Text »|PDF »
Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response.
A. F. Carlin, S. Uchiyama, Y.-C. Chang, A. L. Lewis, V. Nizet, and A. Varki (2009)
Blood
113, 3333-3336
|Abstract »|Full Text »|PDF »
Regulation of streptokinase expression by CovR/S in Streptococcus pyogenes: CovR acts through a single high-affinity binding site.
G. Churchward, C. Bates, A. A. Gusa, V. Stringer, and J. R. Scott (2009)
Microbiology
155, 566-575
|Abstract »|Full Text »|PDF »
Amicus or Adversary: Platelets in Lung Biology, Acute Injury, and Inflammation.
F. A. Bozza, A. M. Shah, A. S. Weyrich, and G. A. Zimmerman (2009)
Am. J. Respir. Cell Mol. Biol.
40, 123-134
|Abstract »|Full Text »|PDF »
Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation.
Y. Wang, M. Li, S. Stadler, S. Correll, P. Li, D. Wang, R. Hayama, L. Leonelli, H. Han, S. A. Grigoryev, et al. (2009)
J. Cell Biol.
184, 205-213
|Abstract »|Full Text »|PDF »
Biofilm formation by group A Streptococcus: a role for the streptococcal regulator of virulence (Srv) and streptococcal cysteine protease (SpeB).
C. D. Doern, A. L. Roberts, W. Hong, J. Nelson, S. Lukomski, W. E. Swords, and S. D. Reid (2009)
Microbiology
155, 46-52
|Abstract »|Full Text »|PDF »
Neutrophil Elastase Mediates Innate Host Protection against Pseudomonas aeruginosa.
T. O. Hirche, R. Benabid, G. Deslee, S. Gangloff, S. Achilefu, M. Guenounou, F. Lebargy, R. E. Hancock, and A. Belaaouaj (2008)
J. Immunol.
181, 4945-4954
|Abstract »|Full Text »|PDF »
Inhibition of airway proteases in cystic fibrosis lung disease.
M. Griese, M. Kappler, A. Gaggar, and D. Hartl (2008)
Eur. Respir. J.
32, 783-795
|Abstract »|Full Text »|PDF »
Advances in Neutrophil Biology: Clinical Implications.
A. S. Cowburn, A. M. Condliffe, N. Farahi, C. Summers, and E. R. Chilvers (2008)
Chest
134, 606-612
|Abstract »|Full Text »|PDF »
Host-Derived Extracellular Nucleic Acids Enhance Innate Immune Responses, Induce Coagulation, and Prolong Survival upon Infection in Insects.
B. Altincicek, S. Stotzel, M. Wygrecka, K. T. Preissner, and A. Vilcinskas (2008)
J. Immunol.
181, 2705-2712
|Abstract »|Full Text »|PDF »
The Capsule Sensitizes Streptococcus pneumoniae to {alpha}-Defensins Human Neutrophil Proteins 1 to 3.
K. Beiter, F. Wartha, R. Hurwitz, S. Normark, A. Zychlinsky, and B. Henriques-Normark (2008)
Infect. Immun.
76, 3710-3716
|Abstract »|Full Text »|PDF »
D-Alanylation of Lipoteichoic Acid Contributes to the Virulence of Streptococcus suis.
N. Fittipaldi, T. Sekizaki, D. Takamatsu, J. Harel, M. d. l. C. Dominguez-Punaro, S. Von Aulock, C. Draing, C. Marois, M. Kobisch, and M. Gottschalk (2008)
Infect. Immun.
76, 3587-3594
|Abstract »|Full Text »|PDF »
Identification of heparin/heparan sulfate interacting protein as a major broad-spectrum antimicrobial protein in lung and small intestine.
U. Meyer-Hoffert, M. Hornef, B. Henriques-Normark, S. Normark, M. Andersson, and K. Putsep (2008)
FASEB J
22, 2427-2434
|Abstract »|Full Text »|PDF »
{beta}-Hydroxybutyrate Abrogates Formation of Bovine Neutrophil Extracellular Traps and Bactericidal Activity against Mammary Pathogenic Escherichia coli.
N. Grinberg, S. Elazar, I. Rosenshine, and N. Y. Shpigel (2008)
Infect. Immun.
76, 2802-2807
|Abstract »|Full Text »|PDF »
Secreted enteric antimicrobial activity localises to the mucus surface layer.
U Meyer-Hoffert, M W Hornef, B Henriques-Normark, L-G Axelsson, T Midtvedt, K Putsep, and M Andersson (2008)
Gut
57, 764-771
|Abstract »|Full Text »|PDF »
Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation.
S. Conus, R. Perozzo, T. Reinheckel, C. Peters, L. Scapozza, S. Yousefi, and H.-U. Simon (2008)
J. Exp. Med.
205, 685-698
|Abstract »|Full Text »|PDF »
Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation.
M. von Kockritz-Blickwede, O. Goldmann, P. Thulin, K. Heinemann, A. Norrby-Teglund, M. Rohde, and E. Medina (2008)
Blood
111, 3070-3080
|Abstract »|Full Text »|PDF »
A Chemokine-Degrading Extracellular Protease Made by Group A Streptococcus Alters Pathogenesis by Enhancing Evasion of the Innate Immune Response.
P. Sumby, S. Zhang, A. R. Whitney, F. Falugi, G. Grandi, E. A. Graviss, F. R. DeLeo, and J. M. Musser (2008)
Infect. Immun.
76, 978-985
|Abstract »|Full Text »|PDF »
Treatment of Experimental Anthrax with Recombinant Capsule Depolymerase.
A. Scorpio, S. A. Tobery, W. J. Ribot, and A. M. Friedlander (2008)
Antimicrob. Agents Chemother.
52, 1014-1020
|Abstract »|Full Text »|PDF »
Acute Lower Respiratory Tract Infection.
J. P. Mizgerd (2008)
N. Engl. J. Med.
358, 716-727
|Full Text »|PDF »
Histone Deimination As a Response to Inflammatory Stimuli in Neutrophils.
Neutrophils efficiently cross-prime naive T cells in vivo.
C. Beauvillain, Y. Delneste, M. Scotet, A. Peres, H. Gascan, P. Guermonprez, V. Barnaba, and P. Jeannin (2007)
Blood
110, 2965-2973
|Abstract »|Full Text »|PDF »
Serine Protease Inhibitor 6-Deficient Mice Have Increased Neutrophil Immunity to Pseudomonas aeruginosa.
M. Zhang, N. Liu, S.-M. Park, Y. Wang, S. Byrne, A. E. Murmann, S. Bahr, M. E. Peter, S. T. Olson, A. Belaaouaj, et al. (2007)
J. Immunol.
179, 4390-4396
|Abstract »|Full Text »|PDF »
Mouse Neutrophils Require JNK2 MAPK for Toxoplasma gondii-Induced IL-12p40 and CCL2/MCP-1 Release.
W. Sukhumavasi, C. E. Egan, and E. Y. Denkers (2007)
J. Immunol.
179, 3570-3577
|Abstract »|Full Text »|PDF »
Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis.
X.-Y. Zhong, I. von Muhlenen, Y. Li, A. Kang, A. K. Gupta, A. Tyndall, W. Holzgreve, S. Hahn, and P. Hasler (2007)
Clin. Chem.
53, 1609-1614
|Abstract »|Full Text »|PDF »
Neutrophil Elastase Converts Human Immature Dendritic Cells into Transforming Growth Factor-{beta}1-Secreting Cells and Reduces Allostimulatory Ability.
P. C. Maffia, S. E. Zittermann, M. L. Scimone, N. Tateosian, N. Amiano, D. Guerrieri, V. Lutzky, D. Rosso, H. E. Romeo, V. E. Garcia, et al. (2007)
Am. J. Pathol.
171, 928-937
|Abstract »|Full Text »|PDF »
Extraintestinal Pathogenic Escherichia coli Survives within Neutrophils.
H. Nazareth, S. A. Genagon, and T. A. Russo (2007)
Infect. Immun.
75, 2776-2785
|Abstract »|Full Text »|PDF »
Cumulative Physiological Events Influence the Inflammatory Response of the Bovine Udder to Escherichia coli Infections During the Transition Period.
C. Burvenich, D. D. Bannerman, J. D. Lippolis, L. Peelman, B. J. Nonnecke, M. E. Kehrli Jr., and M. J. Paape (2007)
J Dairy Sci
90, E39-E54
|Abstract »|Full Text »|PDF »
NK cell activation in visceral leishmaniasis requires TLR9, myeloid DCs, and IL-12, but is independent of plasmacytoid DCs.
U. Schleicher, J. Liese, I. Knippertz, C. Kurzmann, A. Hesse, A. Heit, J. A.A. Fischer, S. Weiss, U. Kalinke, S. Kunz, et al. (2007)
J. Exp. Med.
204, 893-906
|Abstract »|Full Text »|PDF »
The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps.
S. Jaillon, G. Peri, Y. Delneste, I. Fremaux, A. Doni, F. Moalli, C. Garlanda, L. Romani, H. Gascan, S. Bellocchio, et al. (2007)
J. Exp. Med.
204, 793-804
|Abstract »|Full Text »|PDF »
Crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger.
G. Bidla, M. S. Dushay, and U. Theopold (2007)
J. Cell Sci.
120, 1209-1215
|Abstract »|Full Text »|PDF »
Unconventional Roles of the NADPH Oxidase: Signaling, Ion Homeostasis, and Cell Death.
The Nuclease A-Inhibitor Complex Is Characterized by a Novel Metal Ion Bridge.
M. Ghosh, G. Meiss, A. M. Pingoud, R. E. London, and L. C. Pedersen (2007)
J. Biol. Chem.
282, 5682-5690
|Abstract »|Full Text »|PDF »
Novel cell death program leads to neutrophil extracellular traps.
T. A. Fuchs, U. Abed, C. Goosmann, R. Hurwitz, I. Schulze, V. Wahn, Y. Weinrauch, V. Brinkmann, and A. Zychlinsky (2007)
J. Cell Biol.
176, 231-241
|Abstract »|Full Text »|PDF »
Filamentation by Escherichia coli subverts innate defenses during urinary tract infection.
S. S. Justice, D. A. Hunstad, P. C. Seed, and S. J. Hultgren (2006)
PNAS
103, 19884-19889
|Abstract »|Full Text »|PDF »
Deferoxamine reduces tissue damage during endotoxin-induced mastitis in dairy cows..
A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.
M. Shapira, B. J. Hamlin, J. Rong, K. Chen, M. Ronen, and M.-W. Tan (2006)
PNAS
103, 14086-14091
|Abstract »|Full Text »|PDF »
Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection.
M. R. Graham, K. Virtaneva, S. F. Porcella, D. J. Gardner, R. D. Long, D. M. Welty, W. T. Barry, C. A. Johnson, L. D. Parkins, F. A. Wright, et al. (2006)
Am. J. Pathol.
169, 927-942
|Abstract »|Full Text »|PDF »
Vesicles surfing on a lipid bilayer: Self-induced haptotactic motion.
J. Solon, P. Streicher, R. Richter, F. Brochard-Wyart, and P. Bassereau (2006)
PNAS
103, 12382-12387
|Abstract »|Full Text »|PDF »
EPI-hNE4, a Proteolysis-Resistant Inhibitor of Human Neutrophil Elastase and Potential Anti-Inflammatory Drug for Treating Cystic Fibrosis.
S. Attucci, A. Gauthier, B. Korkmaz, P. Delepine, M. F.-D. Martino, F. Saudubray, P. Diot, and F. Gauthier (2006)
J. Pharmacol. Exp. Ther.
318, 803-809
|Abstract »|Full Text »|PDF »
Adaptive response of Yersinia pestis to extracellular effectors of innate immunity during bubonic plague.
F. Sebbane, N. Lemaitre, D. E. Sturdevant, R. Rebeil, K. Virtaneva, S. F. Porcella, and B. J. Hinnebusch (2006)
PNAS
103, 11766-11771
|Abstract »|Full Text »|PDF »
Neutrophil elastase: mediator of extracellular matrix destruction and accumulation..
Polymorphonuclear neutrophils deliver activation signals and antigenic molecules to dendritic cells: a new link between leukocytes upstream of T lymphocytes.
A. M. Megiovanni, F. Sanchez, M. Robledo-Sarmiento, C. Morel, J. C. Gluckman, and S. Boudaly (2006)
J. Leukoc. Biol.
79, 977-988
|Abstract »|Full Text »|PDF »
Salmonella enterica Highly Expressed Genes Are Disease Specific.
G. Lominadze, D. W. Powell, G. C. Luerman, A. J. Link, R. A. Ward, and K. R. McLeish (2005)
Mol. Cell. Proteomics
4, 1503-1521
|Abstract »|Full Text »|PDF »
Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity.
J. H. Cho, I. P. Fraser, K. Fukase, S. Kusumoto, Y. Fujimoto, G. L. Stahl, and R. A. B. Ezekowitz (2005)
Blood
106, 2551-2558
|Abstract »|Full Text »|PDF »
C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation.
L. A. Trouw, S. C. Nilsson, I. Goncalves, G. Landberg, and A. M. Blom (2005)
J. Exp. Med.
201, 1937-1948
|Abstract »|Full Text »|PDF »
Enhanced Pseudomonas aeruginosa Biofilm Development Mediated by Human Neutrophils.
T. S. Walker, K. L. Tomlin, G. S. Worthen, K. R. Poch, J. G. Lieber, M. T. Saavedra, M. B. Fessler, K. C. Malcolm, M. L. Vasil, and J. A. Nick (2005)
Infect. Immun.
73, 3693-3701
|Abstract »|Full Text »|PDF »
Elastolytic Proteases: Inflammation Resolution and Dysregulation in Chronic Infective Lung Disease.
C. C. Taggart, C. M. Greene, T. P. Carroll, S. J. O'Neill, and N. G. McElvaney (2005)
Am. J. Respir. Crit. Care Med.
171, 1070-1076
|Full Text »|PDF »
Fluid- or Surface-Phase Human Salivary Scavenger Protein gp340 Exposes Different Bacterial Recognition Properties.
V. Loimaranta, N. S. Jakubovics, J. Hytonen, J. Finne, H. F. Jenkinson, and N. Stromberg (2005)
Infect. Immun.
73, 2245-2252
|Abstract »|Full Text »|PDF »
Cytosolic Phospholipase A2-{alpha} Is Necessary for Platelet-activating Factor Biosynthesis, Efficient Neutrophil-mediated Bacterial Killing, and the Innate Immune Response to Pulmonary Infection: cPLA2-{alpha} DOES NOT REGULATE NEUTROPHIL NADPH OXIDASE ACTIVITY.
B. B. Rubin, G. P. Downey, A. Koh, N. Degousee, F. Ghomashchi, L. Nallan, E. Stefanski, D. W. Harkin, C. Sun, B. P. Smart, et al. (2005)
J. Biol. Chem.
280, 7519-7529
|Abstract »|Full Text »|PDF »
DNA Binding: a Novel Function of Pseudomonas aeruginosa Type IV Pili.
E. J. van Schaik, C. L. Giltner, G. F. Audette, D. W. Keizer, D. L. Bautista, C. M. Slupsky, B. D. Sykes, and R. T. Irvin (2005)
J. Bacteriol.
187, 1455-1464
|Abstract »|Full Text »|PDF »
Effects of zinc supplementation as adjunct therapy on the systemic immune responses in shigellosis.
M. J Rahman, P. Sarker, S. K Roy, S. M Ahmad, J. Chisti, T. Azim, M. Mathan, D. Sack, J. Andersson, and R. Raqib (2005)
Am. J. Clinical Nutrition
81, 495-502
|Abstract »|Full Text »|PDF »
Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response.
P. Sumby, K. D. Barbian, D. J. Gardner, A. R. Whitney, D. M. Welty, R. D. Long, J. R. Bailey, M. J. Parnell, N. P. Hoe, G. G. Adams, et al. (2005)
PNAS
102, 1679-1684
|Abstract »|Full Text »|PDF »
Methylation of histones in myeloid leukemias as a potential marker of granulocyte abnormalities.
E. Lukasova, Z. Koristek, M. Falk, S. Kozubek, S. Grigoryev, M. Kozubek, V. Ondrej, and I. Kroupova (2005)
J. Leukoc. Biol.
77, 100-111
|Abstract »|Full Text »|PDF »
Contrasting nuclear dynamics of the caspase-activated DNase (CAD) in dividing and apoptotic cells.
Induction of Genes Mediating Interferon-dependent Extracellular Trap Formation during Neutrophil Differentiation.
S. Martinelli, M. Urosevic, A. Daryadel, P. A. Oberholzer, C. Baumann, M. F. Fey, R. Dummer, H.-U. Simon, and S. Yousefi (2004)
J. Biol. Chem.
279, 44123-44132
|Abstract »|Full Text »|PDF »
The Stability of the Nuclear Lamina Polymer Changes with the Composition of Lamin Subtypes According to Their Individual Binding Strengths.