The effect of neutrophil extracellular trap (NETs) on BMDMs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE268729 | GEO | 2024/11/27
REPOSITORIES: GEO
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Project description:The effect of neutrophil extracellular trap (NETs) on BMDMs
| PRJNA1118329 | ENA
Project description:Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. In diabetes they are increased and impair wound healing, during which inflammation normally resolves. Atherosclerosis regression, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis regression in diabetes through unresolved inflammation. Objective: To investigate in diabetes the effect of NETs on plaque macrophage inflammation and whether NETs reduction improves atherosclerosis regression. Findings: Transcriptomic profiling of plaque macrophages from NET positive and negative areas in Ldlr-/- mice revealed inflammasome and glycolysis pathway upregulation, indicating a pro-inflammatory phenotype. During atherosclerosis regression in non-diabetic mice, plaque NET content decreased. In contrast, in diabetic mouse plaques NETs were enriched and persisted after lipid-lowering. DNase1 treatment (to degrade NETs) of diabetic mice reduced plaque NETs and macrophage inflammation and improved atherosclerosis regression after lipid-lowering. Conclusions: NETs decline during atherosclerosis regression in non-diabetic mice, but persist in diabetes and impair regression by exacerbating macrophage inflammation. DNase1 reduced diabetic plaque NETs and macrophage inflammation, and restored atherosclerosis resolution after lipid-lowering, despite ongoing hyperglycemia. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid-lowering, these data suggest that NETs contribute to the increased CVD risk in this population.
2020-05-12 | GSE145200 | GEO
Project description:Neutrophils are necessary in mamalian’s life and are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and the entire host response. The release of neutrophil extracellular DNA in innate immune cells provides specific response to bacteria and fungi. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents and activators of immune response through release of the nuclear content into the extracellular space. Although great strides have been made in dissecting cellular and molecular pathways that control NET formation, the exact molecular composition of released NETs has not been elucidated. Here, we open the field of NETOMIC studies through isolation of NETs in combination with shotgun genomics and proteomics. This study reveals the molecular composition of NETs and specific expression regions of NETs induced in a sterile inflammation system. The existence of an in vitro NET isolation model allowed for an unprecedented amount of replicability. Additional studies are needed to verify the specificity of these sequences in the context of human health and disease upon diverse neutrophil microbial challenges.
2022-10-25 | PXD016143 | Pride
Project description:Klebsiella pneumoniae liver abscess (KPLA) is a severe bacterial infection complicated by intrahepatic thrombophlebitis and extrahepatic metastatic infections, leading to high mortality rates. This study investigates the role of neutrophil extracellular traps (NETs) in endothelial injury and disease progression in KPLA. Our findings demonstrate that C3 deposition on NETs significantly contributes to endothelial damage. In a KPLA mouse model, increased C3 levels were observed in the liver, with NETs carrying substantial amounts of C3, disrupting the endothelial barrier and exacerbating liver injury. Treatment with the C3 inhibitor AMY-101 reduced C3 deposition on NETs, alleviated endothelial damage, significantly improved survival, and reduced extrahepatic dissemination, inflammatory infiltration, and lung injury while also suppressing systemic inflammation. Molecular analysis revealed that the TLR4-PI3Kα-AKT signaling pathway is crucial in K. pneumoniae-induced NET formation. Our findings underscore the pivotal role of C3 in NET-mediated endothelial damage and the pathogenesis of KPLA. Thus, targeting C3 deposition on NETs may be a promising therapeutic strategy to reduce endothelial injury, thrombosis, and extrahepatic infections in KPLA without compromising neutrophil antimicrobial function.
2025-03-21 | GSE288691 | GEO
Project description:Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is characterized by flares of sterile arthritis with neutrophil infiltrate and the overproduction of Interleukin (IL)-1β. The purpose of this study was to elucidate the potential role of neutrophil subsets and neutrophil extracellular traps (NETs) in the pathogenesis of PAPA. The transcriptome of PAPA normal-dense neutrophils, autologous LDGs, and healthy control normal-dense neutrophils was characterized using RNASeq. The transcriptome of a PAPA skin biopsy and a healthy control skin sample was elucidated using RNASeq.
2018-10-23 | GSE117168 | GEO
Project description:We performed a comparison of transcriptome between monocyte-derived dendritic cells (moDC) cultured with neutrophil extracellular traps (NETs) from healthy donors or type 1 diabetes (T1D) patients. The source of moDCs is healthy donors and T1D patients
2020-01-07 | GSE143143 | GEO
Project description:To explore the potential profibrotic effect of neutrophil extacellular traps (NETs), we investigated the transcriptional modification that NET stimulation determines in the intestine of patients with Crohn's disease(CD). To this end, primary intestinal fibroblasts derived from the ileum of patients with CD were either coltured with NETs for 24 hours or left untreated. Bulk RNA sequencing (RNA-seq) was performed to evaluate the differentially expressed genes and determine the possible profibrogenic signature of this interaction.
2024-08-14 | GSE236655 | GEO
Project description:ObjectiveThe release of neutrophil extracellular traps (NETs) by hyperactive neutrophils has recently been recognized to play an important role in antiphospholipid syndrome (APS). This study was undertaken to evaluate autoantibodies targeting NETs in patients with primary APS, and to determine their potential functions and clinical associations.MethodsWe measured global anti-NET activity in 76 patients with primary APS, 23 patients with systemic lupus erythematosus without antiphospholipid antibodies (aPL), 11 patients with a history of unprovoked venous thrombosis without aPL, and 44 healthy controls. The ability of APS sera to degrade NETs was also assessed.ResultsWe found markedly elevated levels of anti-NET IgG and IgM in patients with primary APS compared with healthy controls (for IgG, mean ± SD optical density 0.55 ± 0.34 versus 0.33 ± 0.17; for IgM, mean ± SD optical density 0.76 ± 0.51 versus 0.26 ± 0.23). This anti-NET activity did not correlate with levels of traditional aPL and was relatively stable over time. Mechanistically, anti-NET antibodies (especially of the IgG isotype) impaired the ability of patient sera to degrade NETs (r = 0.4, P = 0.003). Levels of anti-NET IgM inversely correlated with complement C4 (r = 0.4, P = 0.019). Clinically, anti-NET antibodies associated with certain APS clinical manifestations, and in particular recurrent venous thrombosis (odds ratio 4.3; P = 0.002). Interestingly, anti-NET antibody levels also appeared to be associated with unprovoked venous thrombosis in the general population (for IgM, mean ± SD optical density 0.67 ± 0.34 versus 0.26 ± 0.23).ConclusionOur data indicate high levels of anti-NET antibodies in patients with primary APS, which may impair NET clearance and activate the complement cascade. These findings may ultimately enable more effective risk stratification.
| S-EPMC7722115 | biostudies-literature
Project description:Ischemia reperfusion injury (IRI) is a common disease encountered in clinical practice, especially in the management of patients experiencing shock and the treatment of patients with cerebral infarction, and it is also an important factor in the poor prognosis of patients with cardiopulmonary resuscitation or stroke. Therefore, in this study, we constructed rat MCAO models and treated them with NMN. The tissues was collected for RNAseq to explore the gene expression and pathways influenced by NMN. We detected the neutrophil content by flow cytometry, apoptosis was detected by TUNEL staining and flow cytometry, the formation of NETs was evaluated by quantification of NE-DNA, and qPCR and Western blotting were performed to detect the expression of related genes. Our results showed there were fewer apoptotic cells after NMN treatment, and the ROS production was decreased. Importantly, the neutrophil was decreased and NETs were reduced after NMN treatment. Meanwhile, we observed the levels of p-ERK and p-p38 were decreased. Our findings indicated that NMN reduced cerebral ischemia reperfusion injury in rat MCAO model. NMN treatment decreased neutrophil and reduced NETs formation. The mechanism was referred to as the inhibition effect of ROS and ERK/p38 signaling.
2024-10-14 | GSE279377 | GEO
Project description:Extracellular traps (NETs) are released by neutrophils during inflammation and play a role in pathology of diseases such as atherosclerosis, as well as their innate immune function of clearing infection. NETs are composed of a mesh of DNA and histones and contain various anti-microbial granule proteins, such as myeloperoxidase (MPO), which remains enzymatically active. This can result in the production of the reactive oxidant hypochlorous acid (HOCl), which reacts readily with proteins. However, whether histones and other NET-associated proteins contain HOCl-modified proteins is unknown. This is significant as recent studies show that exposure of histones to HOCl alters their extracellular reactivity to promote inflammatory signaling in vascular cells. In this study, we used a proteomic approach to characterise the protein composition of NETs and examine whether histones and other proteins contain oxidative protein-translational modifications resulting from reactions with HOCl. NETs were collected from neutrophil-like PLB-985 cells and primary neutrophils stimulated with phorbol myristate acetate (PMA) or nigericin, a bacterial peptide derived from Streptomyces hygroscopicus. Exposure of proteins to HOCl results in the formation of nitrile and aminoadipic semialdehyde formation on lysine residues, chlorination of tyrosine and tryptophan residues together with methionine oxidation products. Evidence was obtained for the presence of tyrosine chlorination on histones, particularly histone H4, and other proteins like quinone oxidoreductase. Other PTMs, including citrullination and acetylation were also detected on histones (H1, H2A, H3 and H4). Chlorination of the histone H4 peptide TVTAMDVVYALK(R) by HOCl was more abundant in NETs obtained from neutrophils exposed to PMA compared to nigericin, consistent with nigericin triggering NET release via a non-oxidative pathway. Current studies are investigating whether histone modifications occur before or after release from the cell. These findings provide the first evidence that HOCl induces histone modifications on NETs, which may be relevant in disease.
2025-05-30 | PXD060348 | Pride