Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis

ABSTRACT: Disseminated intravascular coagulation (DIC) is a deadly complication of sepsis lacking effective managements. Although excessive inflammatory responses are emerging as key triggers of coagulopathy in sepsis, the interplays between immune system and coagulation are not fully understood. In a murine model of sepsis induced by intraperitoneal lipopolysaccharide (LPS), we found neutrophils in circulation mitigate the occurrence of DIC, thereby preventing the subsequent septic death. We found circulating neutrophils constantly release extracellular vesicles (EVs) containing mitochondria, which carry substantial amount of Superoxide Dismutase 2 (Sod2) upon LPS exposure. The extracellular Sod2 is necessary to bring about neutrophils’ antithrombotic function by eliminating endothelial reactive oxygen species (ROS) accumulation and alleviating endothelial dysfunction. Intervening endothelial ROS accumulation by antioxidants significantly ameliorates DIC with correspondingly improved survival in sepsis. These findings revealed a novel interaction between neutrophils and vascular endothelium which critically regulates coagulation in sepsis and had potential implications for the management of septic DIC.

ORGANISM(S): Mus musculus

PROVIDER: GSE206825 | GEO | 2022/07/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional response in a sepsis mouse model reflects transcriptional response in sepsis patients

Project description:Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under debate. Here we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it with that of human cells stimulated in vitro with LPS on the one hand, and with that of blood cells in septic patients on the other hand. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is a significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes up-regulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes up-regulated in mouse cells stimulated with LPS are enriched in genes up-regulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.

2021-12-31 | GSE185150 | GEO

Marked alterations of neutrophil functions during sepsis-induced immunosuppression

Project description:Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Methods: Peripheral blood was collected from 9 septic shock patients at D3-4 and D6-8 presenting with features of sepsis-induced immunosuppression and compared to 8 healthy controls. Results: In order to get on overview of potential neutrophil alterations after sepsis, we performed transcriptomic analyses on purified neutrophils from 9 septic shock patients and 8 healthy volunteers. For each time point, comparisons were made between patients and controls. Venn diagrams indicated that 364 up-regulated genes and 328 down-regulated genes were common between the two analyses (Supplementary Tables 1 and 2). Interestingly, most of the differentially expressed genes are involved in cell maturation (CD177), apoptosis (STK4, Caspase 8), cell recruitment and chemotaxis (CD44, TPST, MMP9, CREB1), and antimicrobial properties (ARG1, STOM, ADAM9, CD63, YKL40) of neutrophils. Conclusions: The aim of the current study was to perform an extensive investigation of neutrophil alterations during sepsis-induced immunosuppression through phenotypic, functional and transcriptomic studies. Notably, transcriptomic study on purified neutrophils revealed differentially expressed genes between septic patients and healthy volunteers.

2015-12-28 | GSE64457 | GEO

H3K4me3-marked histone orchestrates neutrophil plasticity from immunity to tissue regeneration

Project description:In this study, we used chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3-marked, to identify various TSSs associated with LPS-, TNF-alfa- and IL-10-stimulated neutrophils from healthy individuals, as well as neutrophils derived from the patients with sepsis (systemic septic inflammation with LPS-stimulated neutrophils), NMOSD (aseptic inflammation with neutrophils pre-activated by TNF-alfa and periodontitis (localized self-limiting septic inflammation with IL-10-positive neutrophils). We provided comprehensive epigenomic analysis within H3K4me3- marked histone that allowed us to identify human neutrophil regulators affecting their plasticity during inflammation as well as suppression.

2021-10-27 | GSE186508 | GEO

Stimulation by LPS and HMGB1 in peripheral blood neutrophils from patients with sepsis-induced acute lung injury

Project description:Peripheral blood neutrophils were isolated from septic patients and treated in vitro with LPS or HMGB1 Keywords: ordered

2006-08-01 | GSE3037 | GEO

Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis

Project description:Extracellular cold-inducible RNA-binding protein (eCIRP) is a key mediator of severity and mortality in sepsis. We found that stimulation of mouse bone marrow–derived neutrophils (BMDNs) with eCIRP generated a distinct neutrophil subpopulation, characterized by cell surface markers of both antigen-presenting cells and aged neutrophils as well as expression of IL-12, which we named antigen-presenting aged neutrophils (APANs). The frequency of APANs was significantly increased in the blood, spleen, and lungs of WT mice subjected to cecal ligation and puncture–induced sepsis but not in CIRP–/– mice. Patients with sepsis had a significant increase in circulating APAN counts compared with healthy individuals. Compared with non–APAN-transferred mice, APAN-transferred septic mice had increased serum levels of injury and inflammatory markers, exacerbated acute lung injury (ALI), and worsened survival. APANs and CD4+ T cells colocalized in the spleen, suggesting an immune interaction between these cells. APANs cocultured with CD4+ T cells significantly induced the release of IFN-γ via IL-12. BMDNs stimulated with eCIRP and IFN-γ underwent hyper-NETosis. Stimulating human peripheral blood neutrophils with eCIRP also induced APANs, and stimulating human neutrophils with eCIRP and IFN-γ caused hyper-NETosis. Thus, eCIRP released during sepsis induced APANs to aggravate ALI and worsen the survival of septic animals via CD4+ T cell activation, Th1 polarization, and IFN-γ–mediated hyper-NETosis.

2023-09-27 | GSE228482 | GEO

Expression analysis of altered neutrophils from septic mice

Project description:Neutrophils are critical for effective anti-fungal immune responses. However, in fungal sepsis neutrophils undergo a phenotypical (Ly6G downregulation) and functional alteration (defective ROS production), impairing their anti-fungal capacity. Therefore we wish to characterize the neutrophils in septic mice transcriptionally to describe their role in driving sepsis. We included several control groups. Mice that lack T cells (TCRaKO mice) have increased resistance to the infection and their neutrophils appear unaltered. We identified G-CSF and DNA/histones to be responsible for affecting granulopoiesis, as rG-CSF and Clodronate liposomes combined expand Ly6Glow neutrohils in naive mice.

2021-10-01 | GSE160301 | GEO

A neutrophil - B-cell axis impacts tissue damage control during sepsis via Cxcr4

Project description:Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multi-organ failure. Therapeutic options to prevent sepsis-associated immunopathology remain scarce. Here, we established a mouse model of long-lasting disease tolerance during severe sepsis, manifested by diminished immunothrombosis and organ damage in spite of a high pathogen burden. We found that, both neutrophils and B cells emerged as key regulators of tissue integrity. Enduring changes in the transcriptional profile of neutrophils, included upregulated Cxcr4 expression in protected, tolerant hosts. Neutrophil Cxcr4 upregulation required the presence of B cells, suggesting that B cells promoted disease tolerance by improving tissue damage control via the suppression of neutrophils’ tissue damaging properties. Finally, therapeutic administration of a Cxcr4 agonist successfully promoted tissue damage control and prevented liver damage during sepsis. Our findings highlight the importance of a critical B-cell/neutrophil interaction during sepsis and establish neutrophil Cxcr4 activation as a potential means to promote disease tolerance during sepsis.

2022-08-04 | GSE210207 | GEO

Transcription profiling ofhuman pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum

Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.

2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress

Proteomic analysis of human sepsis monocytes

Project description:In this project we performed a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via label-free shotgun proteomics. We enrolled adult (≥18 years old) patients with sepsis from community-acquired infections, diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria. Blood samples were obtained within the first 72 hours from the diagnosis of sepsis (sepsis phase) and on de day before ICU discharge (recovery phase). The Control group consisted of age matched healthy volunteers. We excluded subjects with AIDS, advanced cancer, hematological diseases, and pregnancy.

2021-09-07 | PXD023938 | Pride

Sepsis Express IG

Project description:The peripheral whole-blood transcriptome analysis has been used to the identification of biomarkers in different clinical syndromes. The ability to simultaneously measure the gene expression levels of the whole transcriptome is providing a broader view of clinical syndromes such as sepsis. The aim of this study was to assess the gene expression profiles of post-surgical patients with septic shock compared with patients without sepsis.

2014-03-15 | E-MTAB-1548 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data