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Neutrophil extracellular traps and DNases orchestrate formation of peritoneal adhesions

Peritoneal adhesions are poorly understood but highly prevalent conditions that can cause intestinal obstruction and pelvic pain requiring surgery. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the molecular processes of their formation still remain elusive...

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Main Authors: Elrod, Julia (Author) , Heuer, Annika (Author) , Knopf, Jasmin (Author) , Schoen, Janina (Author) , Schönfeld, Lavinia (Author) , Trochimiuk, Magdalena (Author) , Stiel, Carolin (Author) , Appl, Birgit (Author) , Raluy, Laia Pagerols (Author) , Saygi, Ceren (Author) , Zlatar, Leticija (Author) , Hosari, Sami (Author) , Royzman, Dmytro (Author) , Winkler, Thomas H. (Author) , Lochnit, Günter (Author) , Leppkes, Moritz (Author) , Grützmann, Robert (Author) , Schett, Georg (Author) , Tomuschat, Christian (Author) , Reinshagen, Konrad (Author) , Herrmann, Martin (Author) , Fuchs, Tobias A. (Author) , Boettcher, Michael (Author)
Format: Article (Journal)
Language:English
Published: 15 December 2023
In: iScience
Year: 2023, Volume: 26, Issue: 12, Pages: 1-17
ISSN:2589-0042
DOI:10.1016/j.isci.2023.108289
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.isci.2023.108289
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004223023660
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Author Notes:Julia Elrod, Annika Heuer, Jasmin Knopf, Janina Schoen, Lavinia Schönfeld, Magdalena Trochimiuk, Carolin Stiel, Birgit Appl, Laia Pagerols Raluy, Ceren Saygi, Leticija Zlatar, Sami Hosari, Dmytro Royzman, Thomas H. Winkler, Günter Lochnit, Moritz Leppkes, Robert Grützmann, Georg Schett, Christian Tomuschat, Konrad Reinshagen, Martin Herrmann, Tobias A. Fuchs, and Michael Boettcher
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Summary:Peritoneal adhesions are poorly understood but highly prevalent conditions that can cause intestinal obstruction and pelvic pain requiring surgery. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the molecular processes of their formation still remain elusive. We performed murine models and analyzed human samples to monitor the formation of adhesions and the treatment with DNases. Various molecular analyses were used to evaluate the adhesions. The experimental peritoneal adhesions of the murine models and biopsy material from humans are largely based on neutrophil extracellular traps (NETs). Treatment with DNASE1 (Dornase alfa) and the human DNASE1L3 analog (NTR-10), significantly reduced peritoneal adhesions in experimental models. We conclude that NETs serve as essential scaffold for the formation of adhesions; DNases interfere with this process. Herein, we show that therapeutic application of DNases can be employed to prevent the formation of murine peritoneal adhesions. If this can be translated into the human situation requires clinical studies.
Item Description:Online verfügbar: 27. OKtober 2023, Artikelversion: 10. November 2023
Gesehen am 08.04.2024
Physical Description:Online Resource
ISSN:2589-0042
DOI:10.1016/j.isci.2023.108289

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