Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma
Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma
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DOI：
10.1165/rcmb.2008-0276oc
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发表时间：
2009-03-01
影响因子：
6.4
通讯作者：
Bonner, James C.
中科院分区：
文献类型：
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作者：
Ryman-Rasmussen, Jessica P.;Tewksbury, Earl W.;Bonner, James C.
由于职业或环境暴露可能带来的健康风险，碳纳米管正受到越来越多的关注。本研究验证了吸入多壁碳纳米管（MWCNT）会增加过敏性哮喘小鼠气道纤维化的假设。将正常小鼠和卵清蛋白致敏小鼠暴露于MWCNT气雾剂（100 mg/m3）或盐水气雾剂6小时。在吸入后1天和14天，通过组织病理学、临床化学、ELISA或RT-PCR检测细胞因子/趋化因子、生长因子和胶原蛋白，检查肺损伤、炎症和纤维化。吸入多壁碳纳米管分布在整个肺，并发现在巨噬细胞通过光学显微镜，但也明显的上皮细胞通过电子显微镜。定量形态测定显示，在14天的小鼠中，接受卵清蛋白和多壁碳纳米管的组合，但不是在小鼠中，只接受卵清蛋白或多壁碳纳米管的显着气道纤维化。未吸入多壁碳纳米管的卵清蛋白致敏小鼠肺灌洗液中IL-13和转化生长因子（TGF）-β 1水平升高，但血小板衍生生长因子（PDGF）-AA水平不变。相反，吸入多壁碳纳米管的未致敏小鼠的PDGF-AA水平升高，但TGF-β 1和IL-13水平没有增加。这表明，由卵清蛋白致敏和多壁碳纳米管吸入联合引起的气道纤维化需要PDGF（一种有效的成纤维细胞有丝分裂原）和TGF-β 1（刺激胶原蛋白产生）。联合卵清蛋白致敏和多壁碳纳米管吸入也协同增加IL-5 mRNA水平，这可能进一步促进气道纤维化。这些数据表明，吸入的MWCNT需要预先存在的炎症引起气道纤维化。我们的研究结果表明，预先存在过敏性炎症的个体可能对吸入多壁碳纳米管引起的气道纤维化易感。
Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and Collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta 1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta 1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta 1, which stimulates Collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.