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ORIGINAL RESEARCH article

Front. Drug Discov.
Sec. Anti-inflammatory and Immunomodulating Agents
Volume 4 - 2024 | doi: 10.3389/fddsv.2024.1404103

The Chronicles of Inflammation: uncovering of distinct patterns of NET degradation products

Provisionally accepted
Janina Schoen Janina Schoen 1Marco Munoz Marco Munoz 1Jasmin Knopf Jasmin Knopf 2Moritz Leppkes Moritz Leppkes 1Dominik Roth Dominik Roth 1Anne Zeitler Anne Zeitler 1Verena Frings Verena Frings 3Bettina Hohberger Bettina Hohberger 1Victoria Zeisberg Victoria Zeisberg 1Luis E. Munoz Luis E. Munoz 1Georg A. Schett Georg A. Schett 1Martin Herrmann Martin Herrmann 1*Christine Schauer Christine Schauer 1
  • 1 University Hospital Erlangen, Erlangen, Bavaria, Germany
  • 2 University Medical Centre Mannheim, University of Heidelberg, Mannheim, Baden-Württemberg, Germany
  • 3 University Hospital Würzburg, Würzburg, Bavaria, Germany

The final, formatted version of the article will be published soon.

    Aims: Neutrophils and neutrophil extracellular traps (NETs) play multifaceted roles in inflammatory diseases. If the balance of NET formation and clearance is disturbed, they contribute to the development and pathogenesis of a plethora of inflammatory diseases. They promote inflammation and tissue degradation, and occlude vessels and ducts. This study focused on the presence of NET remnants generated during the clearance by nucleases and phagocytes.Methods: NET associated parameters in serum and plasma samples from various pathological conditions were investigated. We performed fluorescence-based assays to analyze the concentration of cell free DNA and the activity of neutrophil elastase. The presence of citrullinated histone H3, as well as neutrophil elastase-or myeloperoxidase-DNA complexes were examined employing enzyme-linked immunosorbent assays.We analyzed samples from a variety of inflammatory conditions: (I) the rheumatic autoimmune diseases systemic lupus erythematosus, rheumatoid arthritis, and primary Sjögren's syndrome (II) the inflammatory bowel diseases ulcerative colitis and Crohn's disease (III) hidradenitits suppurativa and (IV) the viral-induced pathologies Coronavirus disease 2019 (COVID-19), and Post COVID Syndrome (PCS). While most NET associated parameters were detected in all inflammatory conditions, certain markers displayed disease-specific patterns. We Gelöscht: degradation markers Gelöscht: NET degradation markers compared the markers in terms of the concentration, correlations with each other and to disease activity, and their impact on sample variability. Systemic lupus erythematosus and rheumatoid arthritis were associated with increased levels of cell free DNA, and citrullinated histone H3 as well as neutrophil elastase-activity, respectively. Samples from patients with COVID-19 were characterized by elevated levels of neutrophil elastase-and myeloperoxidase-DNA complexes.Different diseases are linked to characteristic patterns of NET associated parameters. These patterns offer insights into aberrant NET formation and clearance in different pathologies and may represent key targets for treatment development.

    Keywords: degradation markers, cfDNA, MPO, neurophil elastase, Inflammatory pattern

    Received: 20 Mar 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Schoen, Munoz, Knopf, Leppkes, Roth, Zeitler, Frings, Hohberger, Zeisberg, Munoz, Schett, Herrmann and Schauer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Martin Herrmann, University Hospital Erlangen, Erlangen, 91054, Bavaria, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.