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Role of chemical composition and redox modification of poorly soluble nanomaterials on their ability to enhance allergic airway sensitisation in mice.
Particle and Fibre Toxicology ( IF 7.2 ) Pub Date : 2019-10-28 , DOI: 10.1186/s12989-019-0320-6
Susan Dekkers 1 , James G Wagner 2 , Rob J Vandebriel 1 , Elyse A Eldridge 2 , Selina V Y Tang 3 , Mark R Miller 4 , Isabella Römer 5 , Wim H de Jong 1 , Jack R Harkema 2 , Flemming R Cassee 1, 6
Affiliation  

Engineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice. However, the influence of the different physicochemical properties of these particles on their adjuvant properties is largely unknown. Here we investigate the effects of chemical composition and redox activity of poorly soluble NPs on their adjuvant potency in a mouse model of airway hypersensitivity. NPs of roughly similar sizes with different chemical composition and redox activity, including CeO2, Zr-doped CeO2, Co3O4, Fe-doped Co3O4(using Fe2O3 or Fe3O4) and TiO2 NPs, all showed adjuvant activity. OVA induced immune responses following intranasal exposure of BALB/c mice to 0.02% OVA in combination with 200 μg NPs during sensitization (on day 1, 3, 6 and 8) and 0.5% OVA only during challenge (day 22, 23 and 24) were more pronounced compared to the same OVA treatment regime without NPs. Changes in OVA-specific IgE and IgG1 plasma levels, differential cell count and cytokines in bronchoalveolar lavage fluid (BALF), and histopathological detection of mucosa cell metaplasia and eosinophil density in the conducting airways were observed. Adjuvant activity of the CeO2 NPs was primarily mediated via the Th2 response, while that of the Co3O4 NPs was characterised by no or less marked increases in IgE plasma levels, BALF IL-4 and IL-5 concentrations and percentages of eosinophils in BALF and more pronounced increases in BALF IL-6 concentrations and percentages of lymphocytes in BALF. Co-exposure to Co3O4 NPs with OVA and subsequent OVA challenge also induced perivascular and peribronchiolar lymphoid cell accumulation and formation of ectopic lymphoid tissue in lungs. Responses to OVA combined with various NPs were not affected by the amount of doping or redox activity of the NPs. The findings indicate that chemical composition of NPs influences both the relative potency of NPs to exacerbate allergic airway sensitization and the type of immune response. However, no relation between the acellular redox activity and the observed adjuvant activity of the different NPs was found. Further research is needed to pinpoint the precise physiological properties of NPs and biological mechanisms determining adjuvant activity in order to facilitate a safe-by-design approach to NP development.

中文翻译:

难溶性纳米材料的化学组成和氧化还原修饰对增强小鼠过敏性气道致敏作用的作用。

工程纳米颗粒(NPs)已显示可增强小鼠过敏性气道疾病。但是,这些颗粒的不同理化性质对其佐剂性质的影响在很大程度上是未知的。在这里,我们研究气道超敏性小鼠模型中难溶性NPs的化学成分和氧化还原活性对其佐剂效力的影响。具有不同化学组成和氧化还原活性的大小近似相似的NP,包括CeO2,Zr掺杂的CeO2,Co3O4,Fe掺杂的Co3O4(使用Fe2O3或Fe3O4)和TiO2 NP,均显示出佐剂活性。在致敏过程中(第1、3、6和8天)将BALB / c小鼠鼻内暴露于0.02%OVA与200μgNP组合后,仅在激发过程中(第22天,与没有NP的相同OVA治疗方案相比,图23和24)更为明显。观察到OVA特异性IgE和IgG1血浆水平的变化,支气管肺泡灌洗液(BALF)中差异细胞计数和细胞因子的变化,以及在传导气道中的黏膜细胞化生和嗜酸性粒细胞密度的组织病理学检测。CeO2 NP的佐剂活性主要是通过Th2应答介导的,而Co3O4 NP的佐剂活性的特征是IgE血浆水平,BALF IL-4和IL-5浓度以及嗜酸性粒细胞在BALF中的百分比没有或没有显着增加。 BALF中IL-6浓度和淋巴细胞百分比明显增加。与OVA共同暴露于Co3O4 NPs以及随后的OVA攻击也诱导了肺中血管周围和细支气管周围淋巴样细胞的积累和异位淋巴组织的形成。对OVA结合各种NP的反应不受NP掺杂或氧化还原活性的影响。研究结果表明,NPs的化学成分会影响NPs加剧过敏性气道致敏作用的相对能力以及免疫反应的类型。但是,没有发现脱细胞氧化还原活性和观察到的不同NPs的佐剂活性之间的关系。需要进行进一步的研究以查明NP的确切生理特性和决定佐剂活性的生物学机制,以促进采用安全的设计方法开发NP。对OVA结合各种NP的反应不受NP掺杂或氧化还原活性的影响。研究结果表明,NPs的化学成分会影响NPs加剧过敏性气道致敏作用的相对能力以及免疫反应的类型。但是,没有发现脱细胞氧化还原活性和观察到的不同NPs的佐剂活性之间的关系。需要进行进一步的研究以查明NP的确切生理特性和决定佐剂活性的生物学机制,以促进采用安全的设计方法开发NP。对OVA结合各种NP的反应不受NP掺杂或氧化还原活性的影响。研究结果表明,NPs的化学成分会影响NPs加剧过敏性气道致敏作用的相对能力以及免疫反应的类型。但是,没有发现脱细胞氧化还原活性和观察到的不同NPs的佐剂活性之间的关系。需要进行进一步的研究以查明NP的确切生理特性和决定佐剂活性的生物学机制,以促进采用安全的设计方法开发NP。研究结果表明,NPs的化学成分会影响NPs加剧过敏性气道致敏作用的相对能力以及免疫反应的类型。但是,没有发现脱细胞氧化还原活性和观察到的不同NPs的佐剂活性之间的关系。需要进行进一步的研究以查明NP的确切生理特性和决定佐剂活性的生物学机制,以促进采用安全的设计方法开发NP。研究结果表明,NPs的化学成分会影响NPs加剧过敏性气道致敏作用的相对能力以及免疫反应的类型。但是,没有发现脱细胞氧化还原活性和观察到的不同NPs的佐剂活性之间的关系。需要进行进一步的研究以查明NP的确切生理特性和决定佐剂活性的生物学机制,以促进采用安全的设计方法开发NP。
更新日期:2019-10-28
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