Novel cell death program leads to neutrophil extracellular traps

By T. Fuchs, U. Abed, C. Goosmann, R. Hurwitz, I. Schulze, V. Wahn, Y. Weinrauch, V. Brinkmann, Arturo Zychlinsky. Journal of Cell Biology, 2007

3,208 citations recorded by the source corpus.

Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms. We show that upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and heterochromatin homogenize. Later, the nuclear envelope and the granule membranes disintegrate, allowing the mixing of NET components. Finally, the NETs are released as the cell membrane breaks. This cell death process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/0f05d3c3c4d7915d5c7a9950f65858453d959988

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. P. Kubes
2. Guido Kroemer
3. Arturo Zychlinsky
4. V. Papayannopoulos
5. V. Brinkmann
6. L. Galluzzi
7. N. Borregaard
8. C. Rosales

Citations in the corpus

• A Myeloperoxidase-Containing Complex Regulates Neutrophil Elastase Release and Actin Dynamics during NETosis (2014, neutral): “NETs form in response to specific stimuli through a unique form of cell death called ‘‘NETosis.’’”
• Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis (2012, neutral): “NETosis has been defined previously as part of the innate immune defense against infection (14, 18).”
• COVID-19 and multisystem inflammatory syndrome in children and adolescents (2020, neutral): “83 NETs are a lattice­like web of cell­free DNA, histones, and neutro­ phil granule content including microbicidal proteins and enzymes.”
• Reactive Oxygen Species and Neutrophil Function. (2016, neutral): “Superoxide, hydrogen peroxide, singlet oxygen, and hypochlorous acid have all been implicated (102, 103, 105), but many of these conclusions have relied on adding large doses of oxidant, or nonspecific or inappropriate inhibitors (102).”
• Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance (2017, positive): “…to dissect the role of ROS production in bacterial killing by PMNs, as PMNs employ several bactericidal functions that act downstream of NADPH oxidase activation, including the release of NETs and activation of certain proteases (Reeves et al., 2002; Rada et al., 2004; Fuchs et al., 2007).”
• Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury (2015, positive): “aureus [56], and CGD gene therapy restored NET formation [59], suggesting that ROS are indispensable for NET formation.”
• PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps (2010, positive): “Further, in chronic granulomatous disease patients with impaired nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and reactive oxygen species (ROS) production, neutrophils cannot generate NETs and possess poor antimicrobial activity (Fuchs et al., 2007; Bianchi et al., 2009).”
• Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans (2009, positive): “This could as well be the case in NETs, since the release requires a robust oxidative burst to occur before [6].”
• Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “This would culminate with the extrusion of chromatin fibers intermixed with cytoplasmic and nuclear components, ultimately leading to plasma membrane rupture and RCD [736].”
• Neutrophils, from marrow to microbes. (2010, background): “Large strands of decondensed DNA are extruded from the cell, carrying along with them proteins from cytosol, from granules (which also disintegrated at the same time as the nuclei dissolve), and from chromatin (histones) (Brinkmann and Zychlinsky, 2007; Brinkmann et al., 2004; Fuchs et al., 2007).”
• Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps (2009, neutral): “Moreover, NETs were released in association with cell membrane breaks as a consequence of neutrophil death.(3,10) In contrast, the generation of the mixed extracellular DNA/granule protein structures by eosinophils did not require their cell death.”
• Diverse stimuli engage different neutrophil extracellular trap pathways (2017, positive): “Generation of reactive oxygen species (ROS) is a hallmark of PMA-induced NETosis.”