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Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation
Although many studies have been exploring the mechanisms driving NETs formation, much less attention has been paid to the degradation and elimination of these structures. The NETs clearance and the effective removal of extracellular DNA, enzymatic proteins (neutrophil elastase, proteinase 3, myelope...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002918/ https://www.ncbi.nlm.nih.gov/pubmed/36902325 http://dx.doi.org/10.3390/ijms24054896 |
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author | Demkow, Urszula |
author_facet | Demkow, Urszula |
author_sort | Demkow, Urszula |
collection | PubMed |
description | Although many studies have been exploring the mechanisms driving NETs formation, much less attention has been paid to the degradation and elimination of these structures. The NETs clearance and the effective removal of extracellular DNA, enzymatic proteins (neutrophil elastase, proteinase 3, myeloperoxidase) or histones are necessary to maintain tissue homeostasis, to prevent inflammation and to avoid the presentation of self-antigens. The persistence and overabundance of DNA fibers in the circulation and tissues may have dramatic consequences for a host leading to the development of various systemic and local damage. NETs are cleaved by a concerted action of extracellular and secreted deoxyribonucleases (DNases) followed by intracellular degradation by macrophages. NETs accumulation depends on the ability of DNase I and DNAse II to hydrolyze DNA. Furthermore, the macrophages actively engulf NETs and this event is facilitated by the preprocessing of NETs by DNase I. The purpose of this review is to present and discuss the current knowledge about the mechanisms of NETs degradation and its role in the pathogenesis of thrombosis, autoimmune diseases, cancer and severe infections, as well as to discuss the possibilities for potential therapeutic interventions. Several anti-NETs approaches had therapeutic effects in animal models of cancer and autoimmune diseases; nevertheless, the development of new drugs for patients needs further study for an effective development of clinical compounds that are able to target NETs. |
format | Online Article Text |
id | pubmed-10002918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100029182023-03-11 Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation Demkow, Urszula Int J Mol Sci Review Although many studies have been exploring the mechanisms driving NETs formation, much less attention has been paid to the degradation and elimination of these structures. The NETs clearance and the effective removal of extracellular DNA, enzymatic proteins (neutrophil elastase, proteinase 3, myeloperoxidase) or histones are necessary to maintain tissue homeostasis, to prevent inflammation and to avoid the presentation of self-antigens. The persistence and overabundance of DNA fibers in the circulation and tissues may have dramatic consequences for a host leading to the development of various systemic and local damage. NETs are cleaved by a concerted action of extracellular and secreted deoxyribonucleases (DNases) followed by intracellular degradation by macrophages. NETs accumulation depends on the ability of DNase I and DNAse II to hydrolyze DNA. Furthermore, the macrophages actively engulf NETs and this event is facilitated by the preprocessing of NETs by DNase I. The purpose of this review is to present and discuss the current knowledge about the mechanisms of NETs degradation and its role in the pathogenesis of thrombosis, autoimmune diseases, cancer and severe infections, as well as to discuss the possibilities for potential therapeutic interventions. Several anti-NETs approaches had therapeutic effects in animal models of cancer and autoimmune diseases; nevertheless, the development of new drugs for patients needs further study for an effective development of clinical compounds that are able to target NETs. MDPI 2023-03-03 /pmc/articles/PMC10002918/ /pubmed/36902325 http://dx.doi.org/10.3390/ijms24054896 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Demkow, Urszula Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation |
title | Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation |
title_full | Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation |
title_fullStr | Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation |
title_full_unstemmed | Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation |
title_short | Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation |
title_sort | molecular mechanisms of neutrophil extracellular trap (nets) degradation |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002918/ https://www.ncbi.nlm.nih.gov/pubmed/36902325 http://dx.doi.org/10.3390/ijms24054896 |
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