Institute of Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials Dresden, Leibniz-Institut für Polymerforschung Dresden e.V., Dresden, Germany.
Biomater Sci. 2017 Sep 26;5(10):1998-2008. doi: 10.1039/c7bm00458c.
Neutrophil extracellular trap (NET) formation, a reaction of the innate immune system to fight pathogens, was shown to be involved in thrombus formation. In the present study blood-contacting biomaterials with graded surface characteristics were investigated as a potential cause of NET formation on medical devices. Surface properties are known to govern protein adsorption, cell adhesion and ultimately the activation of several other host defense pathways - potentially also the formation of NETs. Model materials of defined hydrophilic or hydrophobic properties (glass, and thin films of poly(ethylene-alt-maleic anhydride), self-assembled monolayers of methyl terminated alkanethiols, and Teflon AF™) were incubated either with isolated human granulocytes after pre-adsorption with plasma proteins or with human whole blood. NET formation - detected as extracellular DNA, citrullinated histones, elastase and reactive oxygen species (ROS) - was observed on hydrophobic surfaces. Furthermore, NET formation on the hydrophobic surface Teflon AF™ resulted in elevated thrombin generation in hirudin-anticoagulated whole blood, but not in heparinized whole blood. Disintegration of surface-bound NETs by DNase treatment resulted in significantly lower pro-coagulant effects. Thus, NET formation can contribute to the thrombogenicity of clinically applied hydrophobic materials, suggesting NETosis as well as NET surface anchorage as new targets of anticoagulation strategies.
中性粒细胞胞外诱捕网（NET）的形成是先天免疫系统对抗病原体的反应，它被证明与血栓形成有关。在本研究中，具有分级表面特性的血液接触生物材料被研究为医疗器械上 NET 形成的潜在原因。众所周知，表面特性控制着蛋白质的吸附、细胞的黏附，最终激活其他几种宿主防御途径——可能还包括 NET 的形成。具有明确亲水性或疏水性性质的模型材料（玻璃、聚（乙烯--alt-马来酸酐）的薄膜、甲基封端的烷硫醇自组装单层和特氟隆 AF™）在用血浆蛋白预吸附后，要么与分离的人类嗜中性粒细胞一起孵育，要么与人类全血一起孵育。在疏水性表面上观察到 NET 形成 - 作为细胞外 DNA、瓜氨酸化组蛋白、弹性蛋白酶和活性氧物质（ROS）检测到。此外，疏水性表面特氟隆 AF™上的 NET 形成导致在肝素化全血中未升高，但在水蛭素抗凝全血中升高凝血酶生成。通过 DNA 酶处理破坏表面结合的 NET 导致明显较低的促凝作用。因此，NET 形成可能有助于临床应用的疏水性材料的血栓形成性，提示 NET 化和 NET 表面锚定作为抗凝策略的新靶标。
