结肠炎
中性粒细胞胞外陷阱
炎症性肠病
免疫学
血小板
医学
凝结
溃疡性结肠炎
内科学
炎症
化学
疾病
作者
Tao Li,Chunxu Wang,Yingmiao Liu,Baorong Li,Wujian Zhang,Lixiu Wang,Mengxue Yu,Xinyi Zhao,Jingwen Du,Jinming Zhang,Zengxiang Dong,Tao Jiang,Rui Xie,Ruishuang Ma,Shaohong Fang,Jin Zhou,Jialan Shi
出处
期刊:Journal of Crohn's and Colitis
[Oxford University Press]
日期:2019-07-20
卷期号:14 (2): 240-253
被引量:83
标识
DOI:10.1093/ecco-jcc/jjz132
摘要
Abstract Background and Aims Despite the presence of neutrophil extracellular traps [NETs] in inflamed colon having been confirmed, the role of NETs, especially the circulating NETs, in the progression and thrombotic tendency of inflammatory bowel disease [IBD] remains elusive. We extended our previous study to prove that NETs constitute a central component in the progression and prothrombotic state of IBD. Methods In all 48 consecutive patients with IBD were studied. Acute colitis was induced by the treatment of C57BL/6 mice with 3.5% dextran sulphate sodium [DSS] in drinking water for 6 days. Peripheral blood neutrophils and sera were collected from IBD patients and murine colitis models. Exposed phosphatidylserine [PS] was analysed with flow cytometry and confocal microscopy. Procoagulant activity was evaluated using clotting time, purified coagulation complex, and fibrin formation assays. Results We observed higher plasma NET levels and presence of NETs in colon tissue in patients with active IBD. More importantly, NETs were induced in mice with DSS colitis, and inhibition of NET release attenuated colitis as well as colitis-associated tumorigenesis. NET degradation through DNase administration decreased cytokine levels during DSS-induced colitis. In addition, DNase treatment also significantly attenuated the accelerated thrombus formation and platelet activation observed in DSS-induced colitis. NETs triggered PS-positive microparticle release and PS exposure on platelets and endothelial cells partially through TLR2 and TLR4, converting them to a procoagulant phenotype. Conclusions NETs exacerbate colon tissue damage and drive thrombotic tendency during active IBD. Strategies directed against NET formation may offer a potential therapeutic approach for the treatment of IBD.
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