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 hypercoag...

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Main Authors: Shihua Zhang, Mengfan Guo, Qianzi Liu, Jingfeng Liu, Yankun Cui
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
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Online Access:https://doi.org/10.1002/iid3.488
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author Shihua Zhang
Mengfan Guo
Qianzi Liu
Jingfeng Liu
Yankun Cui
author_facet Shihua Zhang
Mengfan Guo
Qianzi Liu
Jingfeng Liu
Yankun Cui
author_sort Shihua Zhang
collection DOAJ
description 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.
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spelling doaj-art-ae32652e8b5b45f78041b70ad19a5eb72025-08-20T03:58:37ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941383139310.1002/iid3.488Neutrophil extracellular traps induce a hypercoagulable state in gliomaShihua Zhang0Mengfan Guo1Qianzi Liu2Jingfeng Liu3Yankun Cui4Department of Neurosurgery of the First Affiliated Hospital Jiamusi University Jiamusi ChinaDepartment of Pathology of the First Affiliated Hospital Jiamusi University Jiamusi ChinaDepartment of Pharmacy of Jiamusi University Jiamusi ChinaDepartment of Outpatient of the First Affiliated Hospital Jiamusi University Jiamusi ChinaDepartment of Neurosurgery of the First Affiliated Hospital Jiamusi University Jiamusi ChinaAbstract 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.https://doi.org/10.1002/iid3.488endothelial cellsgliomaneutrophil extracellular trapsplateletvenous thromboembolism
spellingShingle Shihua Zhang
Mengfan Guo
Qianzi Liu
Jingfeng Liu
Yankun Cui
Neutrophil extracellular traps induce a hypercoagulable state in glioma
Immunity, Inflammation and Disease
endothelial cells
glioma
neutrophil extracellular traps
platelet
venous thromboembolism
title Neutrophil extracellular traps induce a hypercoagulable state in glioma
title_full Neutrophil extracellular traps induce a hypercoagulable state in glioma
title_fullStr Neutrophil extracellular traps induce a hypercoagulable state in glioma
title_full_unstemmed Neutrophil extracellular traps induce a hypercoagulable state in glioma
title_short Neutrophil extracellular traps induce a hypercoagulable state in glioma
title_sort neutrophil extracellular traps induce a hypercoagulable state in glioma
topic endothelial cells
glioma
neutrophil extracellular traps
platelet
venous thromboembolism
url https://doi.org/10.1002/iid3.488
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AT mengfanguo neutrophilextracellulartrapsinduceahypercoagulablestateinglioma
AT qianziliu neutrophilextracellulartrapsinduceahypercoagulablestateinglioma
AT jingfengliu neutrophilextracellulartrapsinduceahypercoagulablestateinglioma
AT yankuncui neutrophilextracellulartrapsinduceahypercoagulablestateinglioma