Cerium oxide nanoparticles, also known as nanoceria, possess antioxidative and anti-inflammatory activities in animal models of inflammatory disorders, such as sepsis. However, it remains unclear how nanoceria affect cellular superoxide fluxes in macrophages, a critical type of cells involved in inflammatory disorders. Using human ML-1 cell-derived macrophages, we showed that nanoceria at 1–100 μg/ml potently reduced superoxide flux from the mitochondrial electron transport chain (METC) in a concentration-dependent manner. The inhibitory effects of nanoceria were also shown in succinate-driven mitochondria isolated from the macrophages. Furthermore, nanoceria markedly mitigated the total intracellular superoxide flux in the macrophages. These data suggest that nanoceria could readily cross the plasma membrane and enter the mitochondrial compartment, reducing intracellular superoxide fluxes in unstimulated macrophages. In macrophages undergoing respiratory burst, nanoceria also strongly reduced superoxide flux from the activated macrophage plasma membrane NADPH oxidase (NOX) in a concentration-dependent manner. Token together, the results of the present study demonstrate that nanoceria can effectively diminish superoxide fluxes from both METC and NOX in human macrophages, which may have important implications for nanoceria-mediated protection against inflammatory disease processes.

氧化铈纳米颗粒，也称为纳米二氧化铈，在脓毒症等炎症性疾病的动物模型中具有抗氧化和抗炎活性。然而，目前尚不清楚纳米纤维素如何影响巨噬细胞中的细胞超氧化物通量，巨噬细胞是一种参与炎症性疾病的关键细胞。使用人 ML-1 细胞来源的巨噬细胞，我们发现 1-100 μg/ml 的纳米纤维素以浓度依赖性方式有效地降低了来自线粒体电子传递链 (METC) 的超氧化物通量。nanoceria 的抑制作用也显示在从巨噬细胞分离的琥珀酸盐驱动的线粒体中。此外，nanoceria 显着减轻了巨噬细胞中的总细胞内超氧化物通量。这些数据表明纳米纤维素可以很容易地穿过质膜并进入线粒体隔室，从而减少未刺激的巨噬细胞中的细胞内超氧化物通量。在经历呼吸爆发的巨噬细胞中，nanoceria 还以浓度依赖性方式强烈降低来自活化的巨噬细胞质膜 NADPH 氧化酶 (NOX) 的超氧化物通量。总之，本研究的结果表明，纳米纤维素可以有效地减少人巨噬细胞中来自 METC 和 NOX 的超氧化物通量，这可能对纳米纤维素介导的针对炎症性疾病过程的保护具有重要意义。nanoceria 还以浓度依赖性方式强烈降低来自活化的巨噬细胞质膜 NADPH 氧化酶 (NOX) 的超氧化物通量。总之，本研究的结果表明，纳米纤维素可以有效地减少人巨噬细胞中来自 METC 和 NOX 的超氧化物通量，这可能对纳米纤维素介导的针对炎症性疾病过程的保护具有重要意义。nanoceria 还以浓度依赖性方式强烈降低来自活化的巨噬细胞质膜 NADPH 氧化酶 (NOX) 的超氧化物通量。总之，本研究的结果表明，纳米纤维素可以有效地减少人巨噬细胞中来自 METC 和 NOX 的超氧化物通量，这可能对纳米纤维素介导的针对炎症性疾病过程的保护具有重要意义。