Neutrophil Extracellular Traps Kill Bacteria

Brinkmann, Volker; Reichard, Ulrike; Goosmann, Christian; Fauler, Beatrix; Uhlemann, Yvonne; Weiss, David S.; Weinrauch, Yvette; Zychlinsky, Arturo

doi:10.1126/science.1092385

Cited by 8,247 publications

(9,086 citation statements)

References 13 publications

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“…Finally, future studies will be necessary to determine whether neutrophil extracellular traps (NETs) are involved in the induction of IFN-α production by PMNs and reciprocally whether circulating chromatin triggers the formation of NETs. Indeed, NETs are structures formed by activated PMNs and contain chromatin [21]. Because they form fibers that bind and kill bacteria, NETs represent a type of innate response.…”

Section: Resultsmentioning

confidence: 99%

Neutrophils and interferon-α-producing cells: who produces interferon in lupus?

Decker

2011

Arthritis Res Ther

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Interferon-α plays a crucial role in the pathogenesis of systemic lupus erythematosus. Nevertheless, the different human cell types producing this cytokine as well as the stimuli inducing its production have not been completely characterized. So far, a subpopulation of dendritic cells activated by immune complexes has been identified as major producers of interferon-α in patients with lupus. However, those cells represent a minor population and some studies have reported the secretion of interferon-α by other cells. On the other hand, more than 50% of blood leukocytes are neutrophils and their functions are still not fully understood. Recent data suggest that neutrophils, though usually not considered interferon-α-producing cells, may represent an unexpected source of this cytokine in response to some lupus stimuli.

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Section: Resultsmentioning

confidence: 99%

Neutrophils and interferon-α-producing cells: who produces interferon in lupus?

Decker

2011

Arthritis Res Ther

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“…Coverslips were rinsed with PBS and then blocked for 45 minutes with PBS in 2% bovine serum albumin (BSA), 2% goat and/or donkey serum, and 0.25% Triton X‐100 3. Primary antibodies were diluted in PBS with 2% BSA and 0.25% Triton X‐100, washed in PBS, revealed using Alexa Fluor– conjugated secondary antibodies, and counterstained with 10 μg/ml Hoechst S769121.…”

Section: Methodsmentioning

confidence: 99%

Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

Spengler

Lugonja

Ytterberg

et al. 2015

Arthritis & Rheumatology

193

172

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ObjectiveIn the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint.MethodsExtracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA.ResultsExtracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis.ConclusionRelease of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA.

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“…In normal cell function, these alter the nature of the histone‐DNA interaction and allow transcription to occur. More recently, controlled histone degradation has been described in neutrophils leading to chromatin decondensation and release of genomic DNA laced with granular proteins as neutrophil extracellular traps (NETs) 6, 7. These meshwork‐like structures promote intravascular thrombosis,8 limit spread of microorganisms, encourage cancer metastasis9 and cause direct injury to adjacent cells 10…”

Section: Introductionmentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

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Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.

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Neutrophil Extracellular Traps Kill Bacteria

Cited by 8,247 publications

References 13 publications

Neutrophils and interferon-α-producing cells: who produces interferon in lupus?

Neutrophils and interferon-α-producing cells: who produces interferon in lupus?

Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

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