Kimball Andrew S, Obi Andrea T, Diaz Jose A, Henke Peter K
Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, Department of Surgery, University of Michigan , Ann Arbor, MI , USA.
Front Immunol. 2016 Jun 27;7:236. doi: 10.3389/fimmu.2016.00236. eCollection 2016.
Venous thrombosis (VT), a leading cause of morbidity and mortality worldwide, has recently been linked to neutrophil activation and release of neutrophil extracellular traps (NETs) via a process called NETosis. The use of various in vivo thrombosis models and genetically modified mice has more precisely defined the exact role of NETosis in the pathogenesis of VT. Translational large animal VT models and human studies have confirmed the presence of NETs in pathologic VT. Activation of neutrophils, with subsequent NETosis, has also been linked to acute infection. This innate immune response, while effective for bacterial clearance from the host by formation of an intravascular bactericidal "net," also triggers thrombosis. Intravascular thrombosis related to such innate immune mechanisms has been coined immunothrombosis. Dysregulated immunothrombosis has been proposed as a mechanism of pathologic micro- and macrovascular thrombosis in sepsis and autoimmune disease. In this focused review, we will address the dual role of NETs in the pathogenesis of VT and immunothrombosis.
静脉血栓形成（VT）是全球发病和死亡的主要原因，最近它通过一种称为中性粒细胞胞外诱捕网（NETs）形成的过程与中性粒细胞活化和NETs释放相关联。使用各种体内血栓形成模型和基因改造小鼠已更精确地确定了NETs形成在VT发病机制中的确切作用。转化性大型动物VT模型和人体研究已证实病理性VT中存在NETs。中性粒细胞活化及随后的NETs形成也与急性感染有关。这种先天免疫反应虽然通过形成血管内杀菌“网”对宿主清除细菌有效，但也会引发血栓形成。与这种先天免疫机制相关的血管内血栓形成被称为免疫性血栓形成。免疫性血栓形成失调已被提出是脓毒症和自身免疫性疾病中病理性微血管和大血管血栓形成的一种机制。在这篇重点综述中，我们将阐述NETs在VT和免疫性血栓形成发病机制中的双重作用。
