From the Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital (C.T.), Karolinska Institutet, Stockholm, Sweden.
Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill (Y.H., N.M.).
Arterioscler Thromb Vasc Biol. 2019 Sep;39(9):1724-1738. doi: 10.1161/ATVBAHA.119.312463. Epub 2019 Jul 18.
Recent studies have demonstrated a role of neutrophils in both venous and arterial thrombosis. A key prothrombotic feature of neutrophils is their ability to release web-like structures composed of DNA filaments coated with histones and granule proteins referred to as neutrophil extracellular traps (NETs). NETs were discovered over a decade ago as part of our first line of host defense against invading microorganisms. Although NETs have a protective role against pathogens, recent data suggest that an uncontrolled and excessive NET formation within the vasculature may contribute to pathological thrombotic disorders. In vitro studies suggest that NETs promote vessel occlusion by providing a scaffold for platelets, red blood cells, extracellular vesicles, and procoagulant molecules, such as von Willebrand factor and tissue factor. In addition, NET components enhance coagulation by both activating the intrinsic pathway and degrading an inhibitor of the extrinsic pathway (tissue factor pathway inhibitor). NET formation has, therefore, been proposed to contribute to thrombus formation and propagation in arterial, venous, and cancer-associated thrombosis. This review will describe animal and human studies suggesting a role of NETs in the pathogenesis of various thrombotic disorders. Targeting NETs may be a novel approach to reduce thrombosis without affecting hemostasis.
最近的研究表明中性粒细胞在静脉和动脉血栓形成中都起作用。中性粒细胞的一个关键促血栓形成特征是它们能够释放由 DNA 丝组成的网状结构，这些 DNA 丝被组蛋白和颗粒蛋白覆盖，称为中性粒细胞胞外诱捕网（NETs）。十多年前，NETs 作为我们抵御入侵微生物的第一道防线的一部分被发现。尽管 NETs 在对抗病原体方面具有保护作用，但最近的数据表明，血管内不受控制和过度的 NET 形成可能导致病理性血栓形成紊乱。体外研究表明，NETs 通过为血小板、红细胞、细胞外囊泡和促凝分子（如血管性血友病因子和组织因子）提供支架，促进血管闭塞。此外，NET 成分通过激活内在途径和降解外在途径（组织因子途径抑制剂）的抑制剂来增强凝血。因此，NET 的形成被提出有助于动脉、静脉和与癌症相关的血栓形成和传播。这篇综述将描述动物和人体研究，表明 NETs 在各种血栓形成紊乱发病机制中的作用。靶向 NETs 可能是一种减少血栓形成而不影响止血的新方法。
