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Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils
Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293572/ https://www.ncbi.nlm.nih.gov/pubmed/27129288 http://dx.doi.org/10.1042/BSR20160031 |
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author | Völlger, Lena Akong-Moore, Kathryn Cox, Linda Goldmann, Oliver Wang, Yanming Schäfer, Simon T. Naim, Hassan Y. Nizet, Victor von Köckritz-Blickwede, Maren |
author_facet | Völlger, Lena Akong-Moore, Kathryn Cox, Linda Goldmann, Oliver Wang, Yanming Schäfer, Simon T. Naim, Hassan Y. Nizet, Victor von Köckritz-Blickwede, Maren |
author_sort | Völlger, Lena |
collection | PubMed |
description | Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone–DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity. |
format | Online Article Text |
id | pubmed-5293572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52935722017-02-14 Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils Völlger, Lena Akong-Moore, Kathryn Cox, Linda Goldmann, Oliver Wang, Yanming Schäfer, Simon T. Naim, Hassan Y. Nizet, Victor von Köckritz-Blickwede, Maren Biosci Rep Original Papers Neutrophil extracellular trap (NET) formation is a significant innate immune defense mechanism against microbial infection that complements other neutrophil functions including phagocytosis and degranulation of antimicrobial peptides. NETs are decondensed chromatin structures in which antimicrobial components (histones, antimicrobial peptides and proteases) are deployed and mediate immobilization of microbes. Here we describe an effect of iron chelation on the phenotype of NET formation. Iron-chelating agent desferrioxamine (DFO) showed a modest but significant induction of NETs by freshly isolated human neutrophils as visualized and quantified by immunocytochemistry against histone–DNA complexes. Further analyses revealed that NET induction by iron chelation required NADPH-dependent production of reactive oxygen species (ROS) as well as protease and peptidyl-arginine-deiminase 4 (PAD4) activities, three key mechanistic pathways previously linked to NET formation. Our results demonstrate that iron chelation by DFO contributes to the formation of NETs and suggest a target for pharmacological manipulation of NET activity. Portland Press Ltd. 2016-05-20 /pmc/articles/PMC5293572/ /pubmed/27129288 http://dx.doi.org/10.1042/BSR20160031 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Papers Völlger, Lena Akong-Moore, Kathryn Cox, Linda Goldmann, Oliver Wang, Yanming Schäfer, Simon T. Naim, Hassan Y. Nizet, Victor von Köckritz-Blickwede, Maren Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils |
title | Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils |
title_full | Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils |
title_fullStr | Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils |
title_full_unstemmed | Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils |
title_short | Iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (NETs) in human blood-derived neutrophils |
title_sort | iron-chelating agent desferrioxamine stimulates formation of neutrophil extracellular traps (nets) in human blood-derived neutrophils |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293572/ https://www.ncbi.nlm.nih.gov/pubmed/27129288 http://dx.doi.org/10.1042/BSR20160031 |
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