LTB4 and 5-oxo-ETE from extracellular vesicles stimulate neutrophils in granulomatosis with polyangiitis.

Surmiak, Marcin; Gielicz, Anna; Stojkov, Darko; Szatanek, Rafał; Wawrzycka-Adamczyk, Katarzyna; Yousefi, Shida; Simon, Hans-Uwe; Sanak, Marek (2020). LTB4 and 5-oxo-ETE from extracellular vesicles stimulate neutrophils in granulomatosis with polyangiitis. Journal of lipid research, 61(1), pp. 1-9. American Society for Biochemistry and Molecular Biology ASBMB 10.1194/jlr.M092072

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Activation of neutrophils is an important mechanism in pathology of granulomatosis with polyangiitis (GPA). In this study, we evaluated if extracellular vesicles (EV) circulating in plasma of GPA patients could contribute to this process. EV from plasma of GPA patients in active stage of the disease (n=10) and healthy controls (n=10) were isolated by ultracentrifugation, characterized by flow cytometry (CD63, CD8) and nanoparticle tracking analysis. Targeted oxylipins lipidomics of EV was performed by HPLC-MS2. EV/oxylipins induced neutrophil extracellular traps (NETs) were analyzed by confocal microscopy and released dsDNA was quantified by PicoGreen fluorescent dye. Reactive oxygen species (ROS) production and neutrophils' EV binding/uptake were evaluated by flow cytometry. Brief priming with granulocyte macrophages-colony stimulating factor (GM-CSF) was required for EV-mediated ROS production and dsDNA release. Priming also increased EV binding/uptake by neutrophils observed, however, only for EV from GPA patients. EV from GPA patients had higher concentrations of leukotriene B4 (LTB4) and 5-oxo-eicosatetraenoic acid (5-oxo-ETE) as compared to EV from healthy controls. Moreover, neutrophils stimulated with LTB4 or 5-oxo-ETE produced ROS and released dsDNA in a concentration-dependent manner. These results reveal the potential role of EVs containing oxylipins cargo on ROS production and NET formation by activated neutrophils.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Stojkov, Darko; Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-2275

Publisher:

American Society for Biochemistry and Molecular Biology ASBMB

Language:

English

Submitter:

Celine Joray

Date Deposited:

17 Dec 2019 10:32

Last Modified:

01 Dec 2020 15:51

Publisher DOI:

10.1194/jlr.M092072

PubMed ID:

31740445

Uncontrolled Keywords:

Eicosanoids Immunology Inflammation Leukotrienes Neutrophils extracellular vesicles granulomatosis with polyangiitis neutrophil extracellular traps reactive oxygen species

BORIS DOI:

10.7892/boris.136952

URI:

https://boris.unibe.ch/id/eprint/136952

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