Neutrophil extracellular traps promote macrophage pyroptosis in sepsis

Chen, Linsong; Zhao, Yanfeng; Lai, Dengming; Zhang, Peng; Yang, Yang; Li, Yuehua; Fei, Ke; Jiang, Gening; Fan, Jie

doi:10.1038/s41419-018-0538-5

Cited by 121 publications

(105 citation statements)

References 37 publications

(43 reference statements)

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“…This latter status was thought to occur through a variety of detrimental factors that consequently lead to immune cell shortage or dysfunction. In recent years, more attention has been attracted to the role of pyroptosis of immune cells in immune disorder of sepsis [6,17,18]. In the current study, we found that the percentages of pyroptotic PBMCs in nonsurvivors were significantly higher than those of the survivors in trauma-induced sepsis.…”

Section: Discussionsupporting

confidence: 54%

Caspase-1-Dependent Pyroptosis of Peripheral Blood Mononuclear Cells Is Associated with the Severity and Mortality of Septic Patients

Wang

Liu

et al. 2020

BioMed Research International

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Purpose. Pyroptosis has been known to play a vital role in the inflammation process which was induced by infection, injury, or inflammatory disease. The present study was aimed at evaluating the percentage of peripheral blood mononuclear cell (PBMC) pyroptosis in septic patients and assessing the correlation of PBMC pyroptosis with the severity and the mortality of septic patients. Methods. 128 trauma-induced patients with sepsis were enrolled in this prospective cohort study. Blood samples were collected, and PBMC pyroptosis was measured by flow cytometry within 24 hours after sepsis was diagnosed. Results. Percentage of PBMC pyroptosis was positively correlated with the acute physiology and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score (all P<0.01). The area under the curve (AUC) for the percentage of PBMC pyroptosis on a receiver operating characteristic curve was 0.79 (95% confidence interval (CI), 0.68–0.90). A Cox proportional hazard model identified an association between an increased percentage of PBMC pyroptosis (>14.17%) and increased risk of the 28-day mortality (hazard ratio=1.234, 95% CI, 1.014–1.502). Conclusion. The percentage of PBMC pyroptosis increases in septic patients, and the increased percentage of PBMC pyroptosis is associated with the severity of sepsis and the 28-day mortality of patients with sepsis.

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Section: Discussionsupporting

confidence: 54%

Caspase-1-Dependent Pyroptosis of Peripheral Blood Mononuclear Cells Is Associated with the Severity and Mortality of Septic Patients

Wang

Liu

et al. 2020

BioMed Research International

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“…Extracellular histones, which have been reported to activate NLRP3 inflammasome (Allam et al, 2013), are associated with a variety of inflammation and diseases. And it has been reported that neutrophil extracellular traps (NETs), in which histone H3 is a key component, can promote macrophage pyroptosis in sepsis (Chen et al, 2018). Once released from the nucleosome, extracellular histones exert their damaging effects in three ways:…”

Section: Discussionmentioning

confidence: 99%

Extracellular Histone H3 Induces Pyroptosis During Sepsis and May Act Through NOD2 and VSIG4/NLRP3 Pathways

Shi

Wang

Chen

et al. 2020

Front. Cell. Infect. Microbiol.

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Background: Histones could be released from the nucleus when stimulated. Increasing evidence has shown that extracellular histones are associated with a variety of inflammation and diseases. Nucleotide binding oligomerzation domain 2 (NOD2) belongs to the NOD like receptor (NLR) family and is reported to promote apoptosis and aggravate inflammatory response. And V-set and immunoglobulin domain containing 4 (VSIG4), a B7 family-related protein, has been confirmed to mediate transcriptional inhibition of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). However, little is known about the impact of extracellular histones on NOD2 or VSIG4 signal transduction. In this study, we aim to explore the effect and mechanism of extracellular histone H3 on pyroptosis. Aim: The purpose of this work was to investigate the mechanism of extracellular histone H3 on pyroptosis in sepsis. Methods: Lipopolysaccharide (LPS) and histone H3 were used to induce sepsis mice model and damage in ANA-1 macrophages. H3 antibody was applied to antagonize the effect of histone H3. NOD2 inhibitor NOD-IN-1 and VSIG4-siRNA were used to investigate the mechanism of histone H3 on pyroptosis. Enzyme linked immune sorbent assay (ELISA) was applied to detect the level of extracellular histone H3. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels. The pathology of tissues was detected. Results: The level of extracellular histone H3 was increased after LPS stimulation. The mRNA and protein levels of NLRP3, caspase-1, gasdermin D (GSDMD), interleukin (IL)-1β, IL-18 were increased in LPS group, but suppressed by H3 antibody. And the expression of NOD2, receptor-interacting protein 2 (RIP2) was elevated compared with control group. The expression of VSIG4 was inhibited by LPS and suppression of H3 promoted the protein level of VSIG4. H3 antibody alleviated pathological damages in tissues. Furthermore, the mRNA and protein levels of NOD2 in H3 group was higher compared with control group. The mRNA and protein levels of VSIG4 in H3 group was decreased compared with control group, but Shi et al. Extracellular Histone H3 Induces Pyroptosis up-regulated by NOD-IN-1. Besides, the mRNA and protein levels of VSIG4 in NOD-IN-1 + VSIG4-siRNA group was elevated compared with VSIG4-siRNA group. Conclusions: Extracellular histone H3 induced by LPS could cause pyroptosis during sepsis via NOD2 and VSIG4/NLRP3 pathway.

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“…The role of cGAS‐STING signaling in the exacerbation of other inflammatory (severe eosinophilic asthma, eosinophilic chronic rhinosinusitis, RA, and psoriasis) diseases associated with the frequent release of extracellular traps needs attention . The release of NETs by neutrophils causes pyroptosis of Mϕs further augmenting the inflammatory process . It will be interesting to observe the impact of Mϕ pyroptosis on the cGAS‐STING signaling pathway in above mentioned autoimmune diseases where NETosis plays a significant role in the immunopathogenesis.…”

Section: Cgas‐sting Signaling In Autoinflammation and Autoimmunitymentioning

confidence: 99%

A STING to inflammation and autoimmunity

Kumar

2019

Journal of Leukocyte Biology

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Various intracellular pattern recognition receptors (PRRs) recognize cytosolic pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Cyclic GMP-AMP synthase (cGAS), a cytosolic PRR, recognizes cytosolic nucleic acids including dsDNAs. The recognition of dsDNA by cGAS generates cyclic GMP-AMP (GAMP). The cGAMP is then recognized by STING generating type 1 IFNs and NF-B-mediated generation of proinflammatory cytokines and molecules. Thus, cGAS-STING signaling mediated recognition of cytosolic dsDNA causing the induction of type 1 IFNs plays a crucial role in innate immunity against cytosolic pathogens, PAMPs, and DAMPs. The overactivation of this system may lead to the development of autoinflammation and autoimmune diseases. The article opens with the introduction of different PRRs involved in the intracellular recognition of dsDNA and gives a brief introduction of cGAS-STING signaling. The second section briefly describes cGAS as intracellular PRR required to recognize intracellular nucleic acids (dsDNA and CDNs) and the formation of cGAMP. The cGAMP acts as a second messenger to activate STING-and TANK-binding kinase 1-mediated generation of type 1 IFNs and the activation of NF-B. The third section of the article describes the role of cGAS-STING signaling in the induction of autoinflammation and various autoimmune diseases. The subsequent fourth section describes both chemical compounds developed and the endogenous negative regulators of cGAS-STING signaling required for its regulation. Therapeutic targeting of cGAS-STING signaling could offer new ways to treat inflammatory and autoimmune diseases. K E Y W O R D S

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Neutrophil extracellular traps promote macrophage pyroptosis in sepsis

Cited by 121 publications

References 37 publications

Caspase-1-Dependent Pyroptosis of Peripheral Blood Mononuclear Cells Is Associated with the Severity and Mortality of Septic Patients

Caspase-1-Dependent Pyroptosis of Peripheral Blood Mononuclear Cells Is Associated with the Severity and Mortality of Septic Patients

Extracellular Histone H3 Induces Pyroptosis During Sepsis and May Act Through NOD2 and VSIG4/NLRP3 Pathways

A STING to inflammation and autoimmunity

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