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Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried.

ABSTRACT: Pregnancy loss is a multidisciplinary problem which concerns researchers from the fields of medicine, epidemiology, psychology, and public health. The primary objective of the present study was to explain the potential role of neutrophil extracellular traps (NETs) in the process of spontaneous miscarriage. Enzyme-linked immunosorbent assay to assess the levels of biomarkers of NETs in the serum of examined women was conducted. Furthermore, levels of nitric oxide (NO) and late markers of its action were measured in serum samples. Analyses results demonstrated the existence of NETs in the placental tissue of women who miscarried as well as a simultaneous increase in the levels of myeloperoxidase and pentraxin 3. This clearly confirms the participation of NETs in the course of pregnancy loss. Women who have had a miscarriage but did not show the presence of NETs in their placenta exhibited the highest contents of NO, nitrotyrosine, and malondialdehyde suggesting a different pathway leading to pregnancy loss associated with disturbed oxidative-antioxidative processes. Although study results demonstrate new aspects associated with the formation of NETs they are not, however, sufficient to unambiguously determine the role of NETs in the course of miscarriage.

SUBMITTER: Omeljaniuk WJ

PROVIDER: S-EPMC7403427 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried.

Omeljaniuk Wioleta Justyna WJ Jabłońska Ewa E Garley Marzena M Pryczynicz Anna A Ratajczak-Wrona Wioletta W Socha Katarzyna K Borawska Maria Halina MH Charkiewicz Angelika Edyta AE

Scientific reports 20200804 1

Pregnancy loss is a multidisciplinary problem which concerns researchers from the fields of medicine, epidemiology, psychology, and public health. The primary objective of the present study was to explain the potential role of neutrophil extracellular traps (NETs) in the process of spontaneous miscarriage. Enzyme-linked immunosorbent assay to assess the levels of biomarkers of NETs in the serum of examined women was conducted. Furthermore, levels of nitric oxide (NO) and late markers of its acti ...[more]

PMID: 32753622

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Project description:BackgroundNeutrophil extracellular trap (NET) formation has been implicated as a pathogenic mechanism in both rheumatoid arthritis (RA) and interstitial lung disease (ILD). However, the role of NETs in RA-associated ILD (RA-ILD) and the mechanisms driving NET formation remain unclear. This study aimed to assess the involvement of NETs in RA-ILD and elucidate the underlying mechanisms.MethodsSingle-cell sequencing was used to identify changes in the quantity and function of neutrophils in the lung tissue of a zymosan A (ZYM)-induced interstitial pneumonia arthritis model. Additionally, nuclear receptor 4A3 (NR4A3) interference was performed in HL-60 cells to assess its impact on NET formation and the transformation of MRC-5 cells into myofibroblasts. The clinical relevance of plasma myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (Cit-H3), and cell-free DNA was evaluated in RA-ILD patients with different imaging types via a commercial enzyme-linked immunosorbent assay (ELISA).ResultsIn the ZYM-treated SKG mouse model, which recapitulates key features of RA-ILD, an increased population of neutrophils in the lung tissue was primarily responsible for NET formation. Mechanistically, we found that interference with NR4A3 expression enhanced NET formation in HL-60 cells, which in turn promoted the differentiation of MRC-5 cells into myofibroblasts. Clinically, plasma MPO-DNA levels are elevated in patients with RA-nonspecific interstitial pneumonia (RA-NSIP), whereas Cit-H3 levels are elevated in RA-usual interstitial pneumonia (RA-UIP) patients compared with healthy subjects. ROC curve analysis further revealed that the combination of plasma MPO-DNA, rheumatoid factor (RF), and anti-citrullinated protein (anti-CCP) and the combination of Cit-H3, RF, and anti-CCP were superior diagnostic panels for NSIP and UIP in RA-ILD patients, respectively. Moreover, compared with those from healthy controls, neutrophils from patients with RA-UIP and RA-NSIP demonstrated a significantly increased ability to form NETs and induce the differentiation of MRC-5 cells into myofibroblasts. Specifically, RA-UIP patients exhibited a greater capacity for NET formation and the differentiation of MRC-5 cells into myofibroblasts than did RA-NSIP patients.ConclusionsThese findings suggest that targeting NETs may be a novel therapeutic approach for treating ILD in RA patients.

Dataset Information

Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried.

Publications

Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried.

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