scholarly journals The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice

2021 ◽  
Author(s):  
Xiaojing Lin ◽  
Yunqi Zhang ◽  
Xiaoling He ◽  
Yan Chen ◽  
Nan Chen ◽  
...  
Keyword(s):  
Biological Function ◽  
Neutrophil Extracellular Traps ◽  
Wild Type ◽  
Placental Development ◽  
Exact Role ◽  
Extracellular Traps ◽  
Cord Plasma ◽  
Newborn Weight ◽  
Placental Thickness

Choline metabolite Trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found the TMAO levels in peripheral and cord plasma were increased in women with GDM, and TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion and angiogenesis of HTR-8/Svneo cells. However, TMAO could not only inhibit the formation of NETs, but also enhance the biological function of HTR-8/Svneo cells. By inducing GDM models in NETs deficient PAD4<sup>-/-</sup> and wild-type mice, the placental weight of PAD4<sup>-/-</sup> mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicated that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO could not only promote the development of the placenta and fetuses, but also inhibit the formation of NETs.

scholarly journals The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice

2021 ◽  
Author(s):  
Xiaojing Lin ◽  
Yunqi Zhang ◽  
Xiaoling He ◽  
Yan Chen ◽  
Nan Chen ◽  
...  
Keyword(s):  
Biological Function ◽  
Neutrophil Extracellular Traps ◽  
Wild Type ◽  
Placental Development ◽  
Exact Role ◽  
Extracellular Traps ◽  
Cord Plasma ◽  
Newborn Weight ◽  
Placental Thickness

Choline metabolite Trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found the TMAO levels in peripheral and cord plasma were increased in women with GDM, and TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion and angiogenesis of HTR-8/Svneo cells. However, TMAO could not only inhibit the formation of NETs, but also enhance the biological function of HTR-8/Svneo cells. By inducing GDM models in NETs deficient PAD4<sup>-/-</sup> and wild-type mice, the placental weight of PAD4<sup>-/-</sup> mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicated that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO could not only promote the development of the placenta and fetuses, but also inhibit the formation of NETs.

scholarly journals Targeting myeloid-cell specific integrin α9β1 inhibits arterial thrombosis in mice

Blood ◽  
2020 ◽  
Vol 135 (11) ◽  
pp. 857-861 ◽  
Author(s):  
Nirav Dhanesha ◽  
Manasa K. Nayak ◽  
Prakash Doddapattar ◽  
Manish Jain ◽  
Gagan D. Flora ◽  
...  
Keyword(s):  
Arterial Thrombosis ◽  
Potential Role ◽  
Myeloid Cell ◽  
Neutrophil Extracellular Traps ◽  
Cathepsin G ◽  
Wild Type ◽  
Extracellular Traps ◽  
Laser Injury ◽  
Activated Platelets

Abstract Evidence suggests that neutrophils contribute to thrombosis via several mechanisms, including neutrophil extracellular traps (NETs) formation. Integrin α9β1 is highly expressed on neutrophils when compared with monocytes. It undergoes affinity upregulation on neutrophil activation, and stabilizes adhesion to the activated endothelium. The role of integrin α9 in arterial thrombosis remains unexplored. We generated novel myeloid cell-specific integrin α9−/− mice (α9fl/flLysMCre+) to study the role of integrin α9 in arterial thrombosis. α9fl/fl littermates were used as controls. We report that α9fl/flLysMCre+ mice were less susceptible to arterial thrombosis in ferric chloride (FeCl3) and laser injury-induced thrombosis models with unaltered hemostasis. Neutrophil elastase-positive cells were significantly reduced in α9fl/flLysMCre+ mice concomitant with reduction in neutrophil count, myeloperoxidase levels, and red blood cells in the FeCl3 injury-induced carotid thrombus. The percentage of cells releasing NETs was significantly reduced in α9fl/flLysMCre+ mouse neutrophils stimulated with thrombin-activated platelets. Furthermore, we found a significant decrease in neutrophil-mediated platelet aggregation and cathepsin-G secretion in α9fl/flLysMCre+ mice. Transfusion of α9fl/fl neutrophils in α9fl/flLysMCre+ mice restored thrombosis similar to α9fl/fl mice. Treatment of wild-type mice with anti-integrin α9 antibody inhibited arterial thrombosis. This study identifies the potential role of integrin α9 in modulating arterial thrombosis.

scholarly journals Neutrophil Extracellular Traps Are Pathogenic in Ventilator-Induced Lung Injury and Partially Dependent on TLR4

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Haosi Li ◽  
Pinhua Pan ◽  
Xiaoli Su ◽  
Shuai Liu ◽  
Lemeng Zhang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Neutrophil Extracellular Traps ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Mechanically Ventilated ◽  
Extracellular Traps ◽  
Ventilator Induced Lung Injury ◽  
Dnase Treatment

The pathogenesis of ventilator-induced lung injury (VILI) is associated with neutrophils. Neutrophils release neutrophil extracellular traps (NETs), which are composed of DNA and granular proteins. However, the role of NETs in VILI remains incompletely understood. Normal saline and deoxyribonuclease (DNase) were used to study the role of NETs in VILI. To further determine the role of Toll-like receptor 4 (TLR4) in NETosis, we evaluated the lung injury and NET formation in TLR4 knockout mice and wild-type mice that were mechanically ventilated. Some measures of lung injury and the NETs markers were significantly increased in the VILI group. DNase treatment markedly reduced NETs markers and lung injury. After high-tidal mechanical ventilation, the NETs markers in the TLR4 KO mice were significantly lower than in the WT mice. These data suggest that NETs are generated in VILI and pathogenic in a mouse model of VILI, and their formation is partially dependent on TLR4.

scholarly journals The state of art of neutrophil extracellular traps in protozoan and helminthic infections

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
César Díaz-Godínez ◽  
Julio C. Carrero
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Parasitic Infections ◽  
Parasitic Diseases ◽  
Helminth Parasites ◽  
Extracellular Traps ◽  
Helminthic Infections ◽  
Bacteria And Fungi ◽  
Net Release

AbstractNeutrophil extracellular traps (NETs) are DNA fibers associated with histones, enzymes from neutrophil granules and anti-microbial peptides. NETs are released in a process denominated NETosis, which involves sequential steps that culminate with the DNA extrusion. NETosis has been described as a new mechanism of innate immunity related to defense against different pathogens. The initial studies of NETs were carried out with bacteria and fungi, but currently a large variety of microorganisms capable of inducing NETs have been described including protozoan and helminth parasites. Nevertheless, we have little knowledge about how NETosis process is carried out in response to the parasites, and about its implication in the resolution of this kind of disease. In the best case, the NETs entrap and kill parasites in vitro, but in others, immobilize the parasites without affecting their viability. Moreover, insufficient studies on the NETs in animal models of infections that would help to define their role, and the association of NETs with chronic inflammatory pathologies such as those occurring in several parasitic infections have left open the possibility of NETs contributing to pathology instead of protection. In this review, we focus on the reported mechanisms that lead to NET release by protozoan and helminth parasites and the evidence that support the role of NETosis in the resolution or pathogenesis of parasitic diseases.

scholarly journals The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Vital Role ◽  
Extracellular Traps ◽  
Protein Components ◽  
Cancer Associated Thrombosis ◽  
Coagulation Pathway

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

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