Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)
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), com...
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doaj-cdf33a1275f14f7f9e1c14bca8663e002021-08-08T11:06:48ZengBMCBMC Immunology1471-21722021-08-0122111410.1186/s12865-021-00442-8Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)Elcha Charles0Benjamin L. Dumont1Steven Bonneau2Paul-Eduard Neagoe3Louis Villeneuve4Agnès Räkel5Michel White6Martin G. Sirois7Research Center, Montreal Heart Institute, Université de MontréalResearch Center, Montreal Heart Institute, Université de MontréalResearch Center, Montreal Heart Institute, Université de MontréalResearch Center, Montreal Heart Institute, Université de MontréalResearch Center, Montreal Heart Institute, Université de MontréalDepartment of Medicine, Université de MontréalResearch Center, Montreal Heart Institute, Université de MontréalResearch Center, Montreal Heart Institute, Université de MontréalAbstract 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.https://doi.org/10.1186/s12865-021-00442-8Angiopoietin 1NeutrophilNETsHeart failureType 2 diabetesCalprotectin (S100A8/A9) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elcha Charles Benjamin L. Dumont Steven Bonneau Paul-Eduard Neagoe Louis Villeneuve Agnès Räkel Michel White Martin G. Sirois |
spellingShingle |
Elcha Charles Benjamin L. Dumont Steven Bonneau Paul-Eduard Neagoe Louis Villeneuve Agnès Räkel Michel White Martin G. Sirois Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs) BMC Immunology Angiopoietin 1 Neutrophil NETs Heart failure Type 2 diabetes Calprotectin (S100A8/A9) |
author_facet |
Elcha Charles Benjamin L. Dumont Steven Bonneau Paul-Eduard Neagoe Louis Villeneuve Agnès Räkel Michel White Martin G. Sirois |
author_sort |
Elcha Charles |
title |
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs) |
title_short |
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs) |
title_full |
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs) |
title_fullStr |
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs) |
title_full_unstemmed |
Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs) |
title_sort |
angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (nets) |
publisher |
BMC |
series |
BMC Immunology |
issn |
1471-2172 |
publishDate |
2021-08-01 |
description |
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. |
topic |
Angiopoietin 1 Neutrophil NETs Heart failure Type 2 diabetes Calprotectin (S100A8/A9) |
url |
https://doi.org/10.1186/s12865-021-00442-8 |
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