title: Oxidative Burst-Dependent NETosis Is Implicated in the Resolution of Necrosis-Associated Sterile Inflammation.
abstract: Necrosis is associated with a profound inflammatory response. The regulation of necrosis-associated inflammation, particularly the mechanisms responsible for resolution of inflammation is incompletely characterized. Nanoparticles are known to induce plasma membrane damage and necrosis followed by sterile inflammation. We observed that injection of metabolically inert nanodiamonds resulted in paw edema in WT andNcf1**mice. However, while inflammation quickly resolved in WT mice, it persisted over several weeks inNcf1**mice indicating failure of resolution of inflammation. Mechanistically, NOX2-dependent reactive oxygen species (ROS) production and formation of neutrophil extracellular traps were essential for the resolution of necrosis-induced inflammation: hence, by evaluating the fate of the particles at the site of inflammation, we observed thatNcf1**mice deficient in NADPH-dependent ROS failed to generate granulation tissue therefore being unable to trap the nanodiamonds. These data suggest that NOX2-dependent NETosis is crucial for preventing the chronification of the inflammatory response to tissue necrosis by forming NETosis-dependent barriers between the necrotic and healthy surrounding tissue.
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Mona H C
authors.initials: MH
authors.lastname: Biermann
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Malgorzata J
authors.initials: MJ
authors.lastname: Podolska
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Knopf
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Reinwald
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Weidner
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Maueröder
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Kienhöfer
authors.affiliation: UMR CNRS 8520, Institut d'Electronique de Microélectronique et de Nanotechnologie (IEMN), Université Lille 1 , Villeneuve d'Ascq , France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Barras
authors.affiliation: UMR CNRS 8520, Institut d'Electronique de Microélectronique et de Nanotechnologie (IEMN), Université Lille 1 , Villeneuve d'Ascq , France.
authors.forename: Rabah
authors.initials: R
authors.lastname: Boukherroub
authors.affiliation: UMR CNRS 8520, Institut d'Electronique de Microélectronique et de Nanotechnologie (IEMN), Université Lille 1 , Villeneuve d'Ascq , France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Szunerits
authors.affiliation: Danylo Halytsky Lviv National Medical University , Lviv , Ukraine.
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Bilyy
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University , Chengdu , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg , Erlangen , Germany.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Munoz
keywords: NETosis; inflammation; nanodiamonds; necrosis; reactive oxygen species; resolution