Neutrophil extracellular traps and DNases orchestrate formation of peritoneal adhesions

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; Michael Boettcher

doi:10.1016/j.isci.2023.108289

Neutrophil extracellular traps and DNases orchestrate formation of peritoneal adhesions

iScience. 2023 Oct 27;26(12):108289. doi: 10.1016/j.isci.2023.108289. eCollection 2023 Dec 15.

Authors

Julia Elrod^{1

2}, Annika Heuer^{1

3}, Jasmin Knopf^{2

4

5}, Janina Schoen^{4

5}, Lavinia Schönfeld¹, Magdalena Trochimiuk¹, Carolin Stiel¹, Birgit Appl¹, Laia Pagerols Raluy¹, Ceren Saygi⁶, Leticija Zlatar^{4

5}, Sami Hosari⁷, Dmytro Royzman⁸, Thomas H Winkler⁸, Günter Lochnit⁹, Moritz Leppkes^{10

5}, Robert Grützmann⁷, Georg Schett^{4

5}, Christian Tomuschat¹, Konrad Reinshagen¹, Martin Herrmann^{4

5}, Tobias A Fuchs², Michael Boettcher^{1

2}

Affiliations

¹ Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
³ Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
⁵ Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
⁶ Bioinformatics Facility, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.
⁸ Division of Genetics, Department of Biology, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
⁹ Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus Liebig University Giessen, Friedrichstrasse 24, Giessen, Germany.
¹⁰ Department of Internal Medicine 1 - Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.

Abstract

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.

Keywords: Biological sciences; Cell biology; Health sciences; Immunology.