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Study on effects and transport of nanoparticles through alveolar wall

纳米颗粒穿过肺泡壁的效应和转运研究

基本信息

批准号：
16390186
负责人：
FURUYAMA Akiko
金额：
$ 5.89万
依托单位：
National Institute for Environmental Studies
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390186/
关键词：
Nano Darticle Inhalation toxicology alveolo-capillarv barrier model translocation alveolar wall

项目摘要

We have prepared an in vitro alveolo-capillary barrier model using alveolar epithelial and endothelial cells to evaluate the behavior of nanoparticles in the respiratory system. Colloidal gold or fluorescent-tagged polystyrene particles of 200 nm and 20 nm were taken up by the alveolar epithelial cells by phagocytosis or endocytosis. Twe hundred nm particles were present only in the alveolar epithelial cells and 20 nm particles were found in the endothelial cells, suggesting that 20 nm but not 200nm particles have an ability to penetrate the alveolo-capillary barrier model. Multi-wall and single-wall carbon nanotubes and 200nm polystyrene particles induced hemeoxygenase-1 in alveolar epithelial cells but 20 nm particles did not. Secretion of cytokines (IL-1β and TNF-α) or activation of NF-κB were not observed. Activation of MAP kinase was observed in cells exposed to carbon nanotubes.To investigate the behavior of nanoparticles deposited in the respiratory airways, we have also complet … More ed an intratracheal instillation study using colloidal gold particles and fluorescent-tagged polystyrene particles (20 nm, 200nm, FluoSphere【○!R】carboxylated-modifiedmicrospheres, red fluorescent 580/605). Most of the particles were found in alveolar macrophages. It is of interest to note that the 20nm particles were present in the microvessel, while the aggregated 20nm and 200nm particles that had been engulfed by alveolar macrophages and alveolar epithelial cells. Alveolar macrophages containing particles were observed in the cavity of heart, the vessel of liver and kidney. ICP-MS analysis revealed that a little amount of gold was detected in blood, heart, liver, kidney, spleen, lymph node after 2 hr instillation.To investigate the effect of nanoparticles deposited in the respiratory airways, we have also completed an intratracheal instillation study using single and maulti-wall carbon nanotubes, fullerene, titanium oxide. Activation of NF-κB were not observed, but upregulation of cytokine secretion (IL-1β, TNF-α, and TGF-β) was detected by instillation of single and multi-wall carbon nanotubes (10 and 50μg/mouse). Instillation of carbon nanotubes induced inflammation, granulomas, and weak fibrosis in lung.These results suggest that nanoparticle of 20 nm may penetrate the alveolar wall (epithelial cells, basement membrane, and endothelial cells) and has a potency to migrate directly into the circulation, although it requires an additional study using electron microscopy to confirm the "Direct migration" scenario. Less

我们利用肺泡上皮细胞和内皮细胞制备了体外肺泡-毛细血管屏障模型，以评估纳米颗粒在呼吸系统中的行为。200 nm和20 nm的胶体金或荧光标记的聚苯乙烯颗粒被肺泡上皮细胞通过吞噬或内吞作用吸收。200 nm的颗粒仅存在于肺泡上皮细胞中，20 nm的颗粒存在于内皮细胞中，这表明20 nm而不是200 nm的颗粒具有穿透肺泡毛细血管屏障模型的能力。多壁和单壁碳纳米管和200 nm的聚苯乙烯颗粒诱导肺泡上皮细胞血红素氧合酶-1，但20 nm的颗粒没有。未观察到细胞因子（IL-1β和TNF-α）的分泌或NF-κB的活化。在暴露于碳纳米管的细胞中观察到MAP激酶的激活。 ...更多信息艾德使用胶体金颗粒和荧光标记的聚苯乙烯颗粒（20 nm，200 nm，FluoSphere[○！R]羧基化修饰的微球，红色荧光580/605）。大部分颗粒存在于肺泡巨噬细胞中。值得注意的是，20 nm的颗粒存在于微血管中，而聚集的20 nm和200 nm的颗粒已被肺泡巨噬细胞和肺泡上皮细胞吞噬。心腔、肝、肾血管内可见含颗粒的肺泡巨噬细胞。ICP-MS分析显示，滴注2小时后，在血液、心脏、肝脏、肾脏、脾脏、淋巴结中检测到少量的金。为了研究纳米颗粒沉积在呼吸道中的效果，我们还完成了单壁和多壁碳纳米管、富勒烯、氧化钛的气管内滴注研究。未观察到NF-κB的活化，但通过滴注单壁和多壁碳纳米管（10和50μg/小鼠）检测到细胞因子分泌（IL-1β、TNF-α和TGF-β）的上调。这些结果表明，20 nm的纳米颗粒可以穿透肺泡壁（上皮细胞、基底膜和内皮细胞），并具有直接迁移到循环中的潜力，尽管需要使用电子显微镜进行额外的研究来证实“直接迁移”的情况。少