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BMC Immunology
Published in: BMC Immunology 1/2021

Open Access 01-12-2021 | Heart Failure | Research

Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)

Authors: Elcha Charles, Benjamin L. Dumont, Steven Bonneau, Paul-Eduard Neagoe, Louis Villeneuve, Agnès Räkel, Michel White, Martin G. Sirois

Published in: BMC Immunology | Issue 1/2021

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Abstract

Background

Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM.

Results

Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin.

Conclusions

Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.
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Metadata
Title
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)
Authors
Elcha Charles
Benjamin L. Dumont
Steven Bonneau
Paul-Eduard Neagoe
Louis Villeneuve
Agnès Räkel
Michel White
Martin G. Sirois
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2021
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-021-00442-8

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