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Polymer‐Coated Metal‐Oxide Nanoparticles Inhibit IgE Receptor Binding Cellular Signaling and Degranulation in a Mast Cell‐like Cell Line

机译:聚合物包覆的金属氧化物纳米颗粒抑制肥大细胞样细胞系中的IgE受体结合细胞信号传导和去颗粒化

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摘要

Previous reports have shown that nanoparticles (NPs) can both enhance and suppress immune effector functions; however the mechanisms that dictate these responses are still unclear. Here, the effects of polyacrylic acid (PAA) functionalized metal‐oxide NP are investigated on RBL‐2H3 (representative mammalian granulocyte‐like cell line) cell viability, cellular degranulation, immunoglobulin E (IgE) receptor binding, and cell signaling pathways related to immune function. The increasing development of PAA‐NPs as pesticide dispersants and as drug carriers in therapeutics necessitates their investigation for safe production. Using two in vitro experimental approaches, this study demonstrates that pre‐exposing RBL‐2H3 cells, or IgE antibodies, to PAA‐NPs (TiO2, CeO2, ZnO, Fe2O3, and PAA‐Capsules (NP coating control) over 24 h, significantly decrease the binding capacity of IgE for Fcε receptors, inhibit the phosphorylation of intracellular signaling proteins (e.g., MAPK ERK) that mediate degranulation, and inhibited RBL‐2H3 cell degranulation. In addition, and unlike the other NPs tested, PAA‐TiO2 significantly reduced RBL‐2H3 viability, in a time (4–24 h) and dose‐dependent manner (>50 μg mL−1). Together, these data demonstrate that PAA‐NPs at sub‐lethal doses can interact with cell surface structures, such as receptors, to suppress various stages of the RBL‐2H3 degranulatory response to external stimuli, and modify immune cell functions that can impact host‐immunity.
机译:先前的报道表明,纳米颗粒(NPs)可以增强和抑制免疫效应子功能。然而,决定这些反应的机制仍不清楚。在这里,研究了聚丙烯酸(PAA)功能化的金属氧化物NP对RBL-2H3(代表性的哺乳动物粒细胞样细胞系)细胞活力,细胞脱粒,免疫球蛋白E(IgE)受体结合以及与之相关的细胞信号通路的影响免疫功能。 PAA-NP作为农药分散剂和在治疗药物中作为药物载体的发展不断,因此需要对其进行安全生产进行研究。使用两种体外实验方法,该研究表明,RBL-2H3细胞或IgE抗体在24小时内预先暴露于PAA-NPs(TiO2,CeO2,ZnO,Fe2O3和PAA-Capsules(NP涂层对照))降低IgE与Fcε受体的结合能力,抑制介导脱粒的细胞内信号蛋白(例如MAPK ERK)的磷酸化,并抑制RBL-2H3细胞脱粒;此外,与其他受测的NP不同,PAA-TiO2显着降低RBL-2H3在一定时间内(4–24 h)的存活率和剂量依赖性(> 50μgmL -1 ),这些数据共同表明,亚致死剂量的PAA-NPs可以与细胞表面结构(例如受体)相互作用,以抑制RBL-2H3对外部刺激脱颗粒反应的各个阶段,并改变可影响宿主免疫力的免疫细胞功能。

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