Calvin, Phoebe, and Joan Snyder Institute for Chronic Disease, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada.
Cell Host Microbe. 2012 Sep 13;12(3):324-33. doi: 10.1016/j.chom.2012.06.011.
During the systemic inflammatory response of severe sepsis, neutrophils accumulate in the liver microcirculation, but their functional significance is largely unknown. We show that neutrophils migrate to liver sinusoids during endotoxemia and sepsis where they exert protective effects by releasing neutrophil extracellular traps (NETs), which are DNA-based structures that capture and eliminate microbes. NETs released into the vasculature ensnare bacteria from the bloodstream and prevent dissemination. NET production requires platelet-neutrophil interactions and can be inhibited by platelet depletion or disruption of integrin-mediated platelet-neutrophil binding. During sepsis, NET release increases bacterial trapping by 4-fold (beyond the basal level provided by resident intravascular macrophages). Blocking NET formation reduces the capture of circulating bacteria during sepsis, resulting in increased dissemination to distant organs. Thus, NETs ensnare circulating bacteria and provide intravascular immunity that protects against bacterial dissemination during septic infections.
在严重脓毒症的全身炎症反应中，中性粒细胞在肝脏微循环中聚集，但它们的功能意义在很大程度上尚不清楚。我们表明，中性粒细胞在内毒素血症和脓毒症期间迁移到肝窦，通过释放中性粒细胞胞外陷阱（NETs）发挥保护作用，NETs 是一种基于 DNA 的结构，可以捕获和消除微生物。释放到脉管系统中的 NET 捕获来自血流的细菌并防止其传播。NET 的产生需要血小板-中性粒细胞相互作用，并且可以通过血小板耗竭或破坏整合素介导的血小板-中性粒细胞结合来抑制。在脓毒症期间，NET 的释放使细菌的捕获增加了 4 倍（超过了常驻血管内巨噬细胞提供的基础水平）。阻止 NET 形成会减少脓毒症期间循环细菌的捕获，从而导致更多细菌播散到远处器官。因此，NET 捕获循环中的细菌，并提供血管内免疫，以防止感染性休克期间细菌的播散。
