| Budget Amount *help |
¥9,200,000 (Direct Cost: ¥9,200,000)
Fiscal Year 2005: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Research Abstract |
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
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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
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