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NETosis Markers in Pregnancy: Effects Differ According to Histone Subtypes
- Source :
- Thrombosis and Haemostasis. 121:877-890
- Publication Year :
- 2021
- Publisher :
- Georg Thieme Verlag KG, 2021.
-
Abstract
- NETosis is an innate immune response occurring after infection or inflammation: activated neutrophils expel decondensed DNA in complex with histones into the extracellular environment in a controlled manner. It activates coagulation and fuels the risk of thrombosis. Human pregnancy is associated with a mild proinflammatory state characterized by circulatory neutrophil activation which is further increased in complicated pregnancies, placenta-mediated complications being associated with an increased thrombotic risk. This aberrant activation leads to an increased release of nucleosomes in the blood flow. The aim of our study was to initially quantify nucleosome-bound histones in normal pregnancy and in placenta-mediated complication counterpart. We analyzed the role of histones on extravillous trophoblast function. Circulating nucleosome-bound histones H3 (Nu.QH3.1, Nu.QH3PanCit, Nu.QH3K27me3) and H4 (Nu.QH4K16Ac) were increased in complicated pregnancies. In vitro using the extravillous cell line HTR-8/SVNeo, we observed that free recombinant H2B, H3, and H4 inhibited migration in wound healing assay, but only H3 also blocked invasion in Matrigel-coated Transwell experiments. H3 and H4 also induced apoptosis, whereas H2B did not. Finally, the negative effects of H3 on invasion and apoptosis could be restored with enoxaparin, a low-molecular-weight heparin (LMWH), but not with aspirin. Different circulating nucleosome-bound histones are increased in complicated pregnancy and this would affect migration, invasion, and induce apoptosis of extravillous trophoblasts. Histones might be part of the link between the risk of thrombosis and pregnancy complications, with an effect of LMWH on both.
- Subjects :
- Adult
Neutrophils
Placenta
Apoptosis
Pilot Projects
Inflammation
Extracellular Traps
Cell Line
Proinflammatory cytokine
Histones
Young Adult
Pre-Eclampsia
Cell Movement
Pregnancy
medicine
Extracellular
Humans
Prospective Studies
Enoxaparin
Innate immune system
Aspirin
biology
business.industry
Hematology
Heparin
Heparin, Low-Molecular-Weight
medicine.disease
Nucleosomes
Trophoblasts
Pregnancy Complications
Kinetics
Histone
biology.protein
Cancer research
Female
France
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 2567689X and 03406245
- Volume :
- 121
- Database :
- OpenAIRE
- Journal :
- Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....49ef47366b8b22ccd2efc82f072eac10