Understanding the biological interactions of graphene-based materials is important for the safe use of these materials. Previous studies have explored the interaction between graphene oxide (GO) and macrophages but not the impact of GO on neutrophils, key cells of the immune system. Here, we synthesized GO sheets with differing lateral dimensions and showed by using an array of analytical and imaging techniques, including transmission and scanning electron microscopy, confocal microscopy, and time-of-flight secondary ion mass spectroscopy (ToF-SIMS), that GO elicited the formation of neutrophil extracellular traps (NETs). ToF-SIMS revealed pronounced perturbations of plasma membrane lipids, including a decrease in cholesterol and increased levels of oxidized cholesterol species. The induction of NETs was size dependent and associated with the production of mitochondrial reactive oxygen species and calcium influx. Importantly, antioxidant treatment reduced the production of NETs. These studies provide evidence that a previously undescribed biological effect of GO manifests through direct effects on membrane lipids.

了解石墨烯基材料的生物相互作用对于安全使用这些材料很重要。先前的研究已经探索了氧化石墨烯（GO）和巨噬细胞之间的相互作用，但没有研究GO对嗜中性粒细胞（免疫系统的关键细胞）的影响。在这里，我们合成了具有不同横向尺寸的GO片材，并通过使用一系列分析和成像技术进行了展示，包括透射和扫描电子显微镜，共聚焦显微镜和飞行时间二次离子质谱（ToF-SIMS），引起中性粒细胞胞外陷阱（NETs）的形成。ToF-SIMS揭示了质膜脂质的明显扰动，包括胆固醇的降低和氧化胆固醇种类的增加。NETs的诱导与大小有关，并与线粒体活性氧的产生和钙的涌入有关。重要的是，抗氧化剂处理减少了NET的产生。这些研究提供了证据，GO的先前未描述的生物学作用是通过对膜脂质的直接作用而显现的。