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Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis
Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We ch...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10016653/ https://www.ncbi.nlm.nih.gov/pubmed/36920946 http://dx.doi.org/10.1371/journal.pone.0282919 |
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author | Lipka, Spyridon Ostendorf, Lennard Schneider, Udo Hiepe, Falk Apel, Falko Alexander, Tobias |
author_facet | Lipka, Spyridon Ostendorf, Lennard Schneider, Udo Hiepe, Falk Apel, Falko Alexander, Tobias |
author_sort | Lipka, Spyridon |
collection | PubMed |
description | Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We characterized the phenotype of neutrophils and their capacity to induce NETs. In addition, the level of circulating NETs, determined by neutrophil elastase/DNA complexes, and the capacity of patient sera to degrade NETs were investigated from blood samples of 12 GPA patients, 21 patients with systemic lupus erythematosus (SLE) and 21 healthy donors (HD). We found that GPA patients had significantly increased levels of low-density granulocytes (LDGs) compared to HD, which displayed an activated and more immature phenotype. While the propensity of normal-density granulocytes to release NETs and the levels of circulating NETs were not significantly different from HD, patient sera from GPA patients degraded NETs less effectively, which weakly correlated with markers of disease activity. In conclusion, increased levels of immature and activated LDGs and altered degradation of circulating NETs may contribute to pathogenesis of GPA, potentially by providing a source of autoantigens that trigger or further enhance autoimmune responses. |
format | Online Article Text |
id | pubmed-10016653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-100166532023-03-16 Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis Lipka, Spyridon Ostendorf, Lennard Schneider, Udo Hiepe, Falk Apel, Falko Alexander, Tobias PLoS One Research Article Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We characterized the phenotype of neutrophils and their capacity to induce NETs. In addition, the level of circulating NETs, determined by neutrophil elastase/DNA complexes, and the capacity of patient sera to degrade NETs were investigated from blood samples of 12 GPA patients, 21 patients with systemic lupus erythematosus (SLE) and 21 healthy donors (HD). We found that GPA patients had significantly increased levels of low-density granulocytes (LDGs) compared to HD, which displayed an activated and more immature phenotype. While the propensity of normal-density granulocytes to release NETs and the levels of circulating NETs were not significantly different from HD, patient sera from GPA patients degraded NETs less effectively, which weakly correlated with markers of disease activity. In conclusion, increased levels of immature and activated LDGs and altered degradation of circulating NETs may contribute to pathogenesis of GPA, potentially by providing a source of autoantigens that trigger or further enhance autoimmune responses. Public Library of Science 2023-03-15 /pmc/articles/PMC10016653/ /pubmed/36920946 http://dx.doi.org/10.1371/journal.pone.0282919 Text en © 2023 Lipka et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lipka, Spyridon Ostendorf, Lennard Schneider, Udo Hiepe, Falk Apel, Falko Alexander, Tobias Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
title | Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
title_full | Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
title_fullStr | Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
title_full_unstemmed | Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
title_short | Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
title_sort | increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10016653/ https://www.ncbi.nlm.nih.gov/pubmed/36920946 http://dx.doi.org/10.1371/journal.pone.0282919 |
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