Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)
Autor: | Benjamin L Dumont, Michel White, Steven Bonneau, Agnès Räkel, Louis Villeneuve, Elcha Charles, Paul-Eduard Neagoe, Martin G. Sirois |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty endocrine system diseases Neutrophils Immunology Inflammation Heart failure 030204 cardiovascular system & hematology Extracellular Traps Exocytosis S100A9 S100A8 03 medical and health sciences 0302 clinical medicine Proteinase 3 Internal medicine Angiopoietin-1 medicine Humans Cells Cultured Aged Aged 80 and over biology Chemistry Angiopoietin 1 Research Calprotectin (S100A8/A9) Neutrophil nutritional and metabolic diseases NETs Type 2 diabetes Neutrophil extracellular traps RC581-607 Immunity Innate 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Myeloperoxidase Neutrophil elastase biology.protein Female Calprotectin medicine.symptom Immunologic diseases. Allergy Leukocyte L1 Antigen Complex |
Zdroj: | BMC Immunology, Vol 22, Iss 1, Pp 1-14 (2021) BMC Immunology |
ISSN: | 1471-2172 |
Popis: | 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. |
Databáze: | OpenAIRE |
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