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Neutrophil extracellular traps induce a hypercoagulable state in glioma.

ABSTRACT:

Background

Venous thromboembolism (VTE) is one of the leading complications in glioma patients. Neutrophil extracellular traps (NETs) have been reported to play a critical role in the physiopathology of cancer. We aimed to investigate the presence and potential role of NETs in the hypercoagulable state in glioma patients. Moreover, we evaluated the interaction between NETs and endothelial cells (ECs) in glioma patients.

Methods

The plasma levels of NETs were detected by enzyme-linked immunosorbent assay. The NET procoagulant activity was performed based on fibrin formation assays. The NET generation and NET-treated ECs in vitro were observed by confocal microscopy. Activated platelets (PLTs) and PLT-neutrophil aggregates were detected by flow cytometry.

Results

Plasma NET markers were significantly higher in stage III/IV glioma patients than in stage I/II glioma patients and healthy subjects. PLTs from glioma patients tended to induce NET formation than those from healthy subjects. NETs contributed to the hypercoagulable state in glioma patients. After ECs were incubated with NETs isolated from stage III/IV glioma patients, they lost their intercellular connections and were converted into procoagulant phenotypes. Combining DNase I and activated protein C markedly decreased endothelial dysfunction.

Conclusions

Our results showed the interaction between NETs and hypercoagulability in glioma patients. Targeting NETs may be a potential therapeutic and prevention direction for thrombotic complications in glioma patients.

SUBMITTER: Zhang S

PROVIDER: S-EPMC8589396 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP-induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are relevant actors in the pathogenesis of sepsis.