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The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation

Eosinophils are a subset of granulocytes characterized by a high abundance of specific granules in their cytoplasm. To act as effector cells, eosinophils degranulate and form eosinophil extracellular traps (EETs), which contain double-stranded DNA (dsDNA) co-localized with granule proteins. The exac...

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Autores principales: Germic, Nina, Fettrelet, Timothée, Stojkov, Darko, Hosseini, Aref, Horn, Michael P., Karaulov, Alexander, Simon, Dagmar, Yousefi, Shida, Simon, Hans-Uwe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913244/
https://www.ncbi.nlm.nih.gov/pubmed/33546138
http://dx.doi.org/10.3390/cells10020306
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author Germic, Nina
Fettrelet, Timothée
Stojkov, Darko
Hosseini, Aref
Horn, Michael P.
Karaulov, Alexander
Simon, Dagmar
Yousefi, Shida
Simon, Hans-Uwe
author_facet Germic, Nina
Fettrelet, Timothée
Stojkov, Darko
Hosseini, Aref
Horn, Michael P.
Karaulov, Alexander
Simon, Dagmar
Yousefi, Shida
Simon, Hans-Uwe
author_sort Germic, Nina
collection PubMed
description Eosinophils are a subset of granulocytes characterized by a high abundance of specific granules in their cytoplasm. To act as effector cells, eosinophils degranulate and form eosinophil extracellular traps (EETs), which contain double-stranded DNA (dsDNA) co-localized with granule proteins. The exact molecular mechanism of EET formation remains unknown. Although the term “EET release” has been used in scientific reports, it is unclear whether EETs are pre-formed in eosinophils and subsequently released. Moreover, although eosinophil degranulation has been extensively studied, a precise time-course of granule protein release has not been reported until now. In this study, we investigated the time-dependent release of eosinophil peroxidase (EPX) and mitochondrial DNA (mtDNA) following activation of both human and mouse eosinophils. Unexpectedly, maximal degranulation was already observed within 1 min with no further change upon complement factor 5 (C5a) stimulation of interleukin-5 (IL-5) or granulocyte/macrophage colony-stimulating factor (GM-CSF)-primed eosinophils. In contrast, bulk mtDNA release in the same eosinophil populations occurred much slower and reached maximal levels between 30 and 60 min. Although no single-cell analyses have been performed, these data suggest that the molecular pathways leading to degranulation and mtDNA release are at least partially different. Moreover, based on these data, it is likely that the association between the mtDNA scaffold and granule proteins in the process of EET formation occurs in the extracellular space.
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spelling pubmed-79132442021-02-28 The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation Germic, Nina Fettrelet, Timothée Stojkov, Darko Hosseini, Aref Horn, Michael P. Karaulov, Alexander Simon, Dagmar Yousefi, Shida Simon, Hans-Uwe Cells Article Eosinophils are a subset of granulocytes characterized by a high abundance of specific granules in their cytoplasm. To act as effector cells, eosinophils degranulate and form eosinophil extracellular traps (EETs), which contain double-stranded DNA (dsDNA) co-localized with granule proteins. The exact molecular mechanism of EET formation remains unknown. Although the term “EET release” has been used in scientific reports, it is unclear whether EETs are pre-formed in eosinophils and subsequently released. Moreover, although eosinophil degranulation has been extensively studied, a precise time-course of granule protein release has not been reported until now. In this study, we investigated the time-dependent release of eosinophil peroxidase (EPX) and mitochondrial DNA (mtDNA) following activation of both human and mouse eosinophils. Unexpectedly, maximal degranulation was already observed within 1 min with no further change upon complement factor 5 (C5a) stimulation of interleukin-5 (IL-5) or granulocyte/macrophage colony-stimulating factor (GM-CSF)-primed eosinophils. In contrast, bulk mtDNA release in the same eosinophil populations occurred much slower and reached maximal levels between 30 and 60 min. Although no single-cell analyses have been performed, these data suggest that the molecular pathways leading to degranulation and mtDNA release are at least partially different. Moreover, based on these data, it is likely that the association between the mtDNA scaffold and granule proteins in the process of EET formation occurs in the extracellular space. MDPI 2021-02-03 /pmc/articles/PMC7913244/ /pubmed/33546138 http://dx.doi.org/10.3390/cells10020306 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Germic, Nina
Fettrelet, Timothée
Stojkov, Darko
Hosseini, Aref
Horn, Michael P.
Karaulov, Alexander
Simon, Dagmar
Yousefi, Shida
Simon, Hans-Uwe
The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation
title The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation
title_full The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation
title_fullStr The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation
title_full_unstemmed The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation
title_short The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation
title_sort release kinetics of eosinophil peroxidase and mitochondrial dna is different in association with eosinophil extracellular trap formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913244/
https://www.ncbi.nlm.nih.gov/pubmed/33546138
http://dx.doi.org/10.3390/cells10020306
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