Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université Du Québec, INRS-Centre Armand-Frappier Santé Biotechnologie, Laval, Québec, Canada.
Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université Du Québec, INRS-Centre Armand-Frappier Santé Biotechnologie, Laval, Québec, Canada.
Chem Biol Interact. 2022 Sep 25;365:110053. doi: 10.1016/j.cbi.2022.110053. Epub 2022 Jul 21.
Iron oxide nanoparticles (FeO NPs) are important for different medical applications. However, potential toxicity has been reported and several parameters must still be studied to reach highest therapeutic efficacy with minimal undesired effects. Inflammation is one of the most reported undesired effects of NP exposure in a variety of inflammatory models and conflicting data exist regarding whether FeO NPs possess pro- or anti-inflammatory activities. The aim of this study was to determine the direct effect of FeO NPs on the biology of neutrophil, a key player cell in inflammation. Freshly isolated human neutrophils were incubated in vitro with FeO NPs, and several functions have been studied. Using transmission electronic microscopy, FeO NPs were found to be ingested by neutrophils. These NPs do not induce a respiratory burst by themselves, but they increase the ability of neutrophils to adhere onto human endothelial cells as well as enhance phagocytosis. An antibody array approach revealed that FeO NPs induce the production of some cytokines, including the chemokine IL-8 (CXCL8), which was confirmed by ELISA. FeONPs were found to delay spontaneous neutrophil apoptosis regardless of sex of the donor. Using a pharmacological approach, we demonstrate that FeO NPs delay apoptosis by a de novo protein synthesis-dependent mechanism and via different cell signalling pathways. The data indicate that FeO NPs can alter the biology of human neutrophils and that they possess some pro-inflammatory effects, particularly based on their capacity to delay apoptosis and to induce the production of pro-inflammatory cytokines. Therefore, FeO NPs can regulate inflammation by targeting human neutrophil functions.
氧化铁纳米颗粒（FeO NPs）在不同的医学应用中非常重要。然而，已经报道了其潜在的毒性，并且仍有几个参数需要研究，以在最小化不良影响的情况下达到最高的治疗效果。炎症是 NP 暴露在各种炎症模型中最常见的不良影响之一，关于 FeO NPs 是否具有促炎或抗炎活性存在相互矛盾的数据。本研究旨在确定 FeO NPs 对中性粒细胞生物学的直接影响，中性粒细胞是炎症中的关键细胞。新鲜分离的人中性粒细胞在体外与 FeO NPs 孵育，并研究了几种功能。通过透射电子显微镜发现，FeO NPs 被中性粒细胞摄取。这些 NPs 本身不会引起呼吸爆发，但它们增加了中性粒细胞与人内皮细胞黏附的能力，并增强了吞噬作用。抗体阵列方法显示，FeO NPs 诱导产生一些细胞因子，包括趋化因子 IL-8（CXCL8），这通过 ELISA 得到了证实。FeO NPs 被发现无论供体的性别如何，都能延迟中性粒细胞的自发凋亡。通过药理学方法，我们证明 FeO NPs 通过依赖新蛋白质合成的机制和通过不同的细胞信号通路来延迟细胞凋亡。这些数据表明，FeO NPs 可以改变人中性粒细胞的生物学特性，并且它们具有一些促炎作用，特别是基于它们延迟细胞凋亡和诱导产生促炎细胞因子的能力。因此，FeO NPs 可以通过靶向人中性粒细胞功能来调节炎症。
