Immune Disease Institute, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15880-5. doi: 10.1073/pnas.1005743107. Epub 2010 Aug 23.
Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis.
中性粒细胞胞外诱捕网（NETs）是机体固有免疫反应的一部分，能够应对感染。NETs 是由 DNA 纤维、组蛋白和抗菌蛋白构成的网状结构。微生物被 NETs 捕获，其局部会遭遇高浓度的、具有细胞毒性的效应蛋白。最近的研究表明，NETs 会在感染和非传染性疾病的血管内形成。在此，我们报告 NETs 为血栓形成提供了一个此前未被识别的支架和刺激物。NETs 与血液混合后会引起血小板黏附、激活和聚集。DNase 或抗凝剂肝素可以破坏 NET 支架，从而阻止血栓形成。用纯化的组蛋白刺激血小板就足以引起聚集。NETs 可以募集红细胞、促进纤维蛋白沉积，并诱导红色血栓形成，如深静脉血栓形成中所见的那样。深静脉血栓形成的狒狒模型中可检测到血栓和血浆中的细胞外 DNA 陷阱标志物，这是炎症增强血栓形成的一个例子。我们的观察结果表明，NETs 是炎症与血栓形成之间以前未被识别的联系，可能进一步解释了感染与血栓形成的流行病学关联。
