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 (2021). The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation. Cells, 10(2) MDPI 10.3390/cells10020306

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Germic, Nina; Fettrelet, Timothée; Stojkov, Darko; Hosseini, Aref; Horn, Michael; Simon, Dagmar; Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2073-4409

Publisher:

MDPI

Language:

English

Submitter:

Celine Joray

Date Deposited:

09 Feb 2021 16:10

Last Modified:

10 Feb 2021 01:35

Publisher DOI:

10.3390/cells10020306

PubMed ID:

33546138

Uncontrolled Keywords:

degranulation eosinophil extracellular traps eosinophil peroxidase eosinophils kinetics mitochondrial DNA

BORIS DOI:

10.48350/152066

URI:

https://boris.unibe.ch/id/eprint/152066

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