PMID- 35869501 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220729 IS - 2045-3701 (Print) IS - 2045-3701 (Electronic) IS - 2045-3701 (Linking) VI - 12 IP - 1 DP - 2022 Jul 22 TI - Neutrophil extracellular traps promote thrombogenicity in cerebral venous sinus thrombosis. PG - 114 LID - 10.1186/s13578-022-00845-z [doi] LID - 114 AB - BACKGROUND: Neutrophil extracellular traps (NETs) contribute to the creation of a coagulation state in various diseases. Currently, it is not clear whether NETs are present in the thrombi and plasma of patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the presence of NETs in thrombi and blood samples from CVST patients and the procoagulant activity (PCA) of NETs during the progression of CVST. RESULTS: Thrombi obtained from CVST patients undergoing thrombectomy were examined by immunochemistry using neutrophil elastase (NE), CD66b and citrullinated histone H3(citH3). The presence of NET markers in samples from 37 CVST patients and 32 healthy people was evaluated by ELISA. NET-producing neutrophils and neutrophil-platelet (PLT) aggregates were examined in samples obtained from CVST patients and healthy people by flow cytometry. The TAT complex in plasma sample from each group was detected by ELISA to evaluate the procoagulant activity of NETs in CVST patients. Neutrophils from healthy subjects were treated with PLT-rich plasma in the presence of anti-PF4 antibodies or an autophagy inhibitor and analyzed by flow cytometry and confocal microscopy. After treatment with NETs, the expression of von Willebrand factor (VWF), tissue factor (TF) and CD31 in human brain microvascular endothelial cells (HBMECs) was measured by confocal microscopy and western blotting. Our results showed that NETs were abundant in the plasma and thrombi from CVST patients. Platelet factor 4 (PF4) from CVST PLTs induced NET generation through autophagy. NETs could induce PCA by modulating TF and phosphatidylserine (PS) in CVST. NETs also disrupted the endothelial barrier and transformed ECs into a procoagulant phenotype to exacerbate thrombogenicity. CONCLUSIONS: NET generation was mediated by PF4 from PLTs through autophagy and contribute to thrombosis in CVST patients. CI - (c) 2022. The Author(s). FAU - Jin, Jiaqi AU - Jin J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Qiao, Shan AU - Qiao S AD - Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. FAU - Liu, Jie AU - Liu J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Li, Wenqiang AU - Li W AD - Department of Vascular Surgery, Jinshan Hospital of Fudan University, Shanghai, China. FAU - Wang, Fang AU - Wang F AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Gao, Xin AU - Gao X AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Tian, Jiawei AU - Tian J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Wang, Nan AU - Wang N AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Zhang, Jiheng AU - Zhang J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Dong, Jiawei AU - Dong J AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. FAU - Li, Haiyun AU - Li H AD - Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Wang, Jianjun AU - Wang J AD - Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. 1499@sdhospital.com.cn. FAU - Hu, Shaoshan AU - Hu S AD - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. shaoshanhu421@163.com. AD - Department of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. shaoshanhu421@163.com. FAU - Zhou, Peng AU - Zhou P AD - Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China. zhoupeng2933@126.com. LA - eng GR - 20214Y0365/Shanghai Municipal Health and Construction Commission Scientific Research Program/ GR - JYQN-JC-202108/the Youth Research Start-up Program of Jinshan Hospital of Fudan Universityb/ PT - Journal Article DEP - 20220722 PL - England TA - Cell Biosci JT - Cell & bioscience JID - 101561195 PMC - PMC9306243 OTO - NOTNLM OT - Cerebral venous sinus thrombosis OT - Coagulation OT - Endothelial dysfunction OT - Neutrophil extracellular traps OT - Platelet factor 4 COIS- The authors declare no conflicts of interest. EDAT- 2022/07/23 06:00 MHDA- 2022/07/23 06:01 PMCR- 2022/07/22 CRDT- 2022/07/22 23:45 PHST- 2022/04/06 00:00 [received] PHST- 2022/07/06 00:00 [accepted] PHST- 2022/07/22 23:45 [entrez] PHST- 2022/07/23 06:00 [pubmed] PHST- 2022/07/23 06:01 [medline] PHST- 2022/07/22 00:00 [pmc-release] AID - 10.1186/s13578-022-00845-z [pii] AID - 845 [pii] AID - 10.1186/s13578-022-00845-z [doi] PST - epublish SO - Cell Biosci. 2022 Jul 22;12(1):114. doi: 10.1186/s13578-022-00845-z.