Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Nanotoxicology. 2011 Dec;5(4):531-45. doi: 10.3109/17435390.2010.530004. Epub 2010 Nov 3.
Cerium oxide (CeO₂) represents an important nanomaterial with wide ranging applications. However, little is known regarding how CeO₂ exposure may influence pulmonary or systemic inflammation. Furthermore, how mast cells would influence inflammatory responses to a nanoparticle exposure is unknown. We thus compared pulmonary and cardiovascular responses between C57BL/6 and B6.Cg-Kit(W-sh) mast cell deficient mice following CeO₂ nanoparticle instillation. C57BL/6 mice instilled with CeO₂ exhibited mild pulmonary inflammation. However, B6.Cg-Kit(W-sh) mice did not display a similar degree of inflammation following CeO₂ instillation. Moreover, C57BL/6 mice instilled with CeO₂ exhibited altered aortic vascular responses to adenosine and an increase in myocardial ischemia/reperfusion injury which was absent in B6.Cg-Kit(W-sh) mice. In vitro CeO₂ exposure resulted in increased production of PGD₂, TNF-α, IL-6 and osteopontin by cultured mast cells. These findings demonstrate that CeO₂ nanoparticles activate mast cells contributing to pulmonary inflammation, impairment of vascular relaxation and exacerbation of myocardial ischemia/reperfusion injury.
氧化铈（CeO₂）是一种具有广泛应用的重要纳米材料。然而，对于氧化铈暴露如何影响肺部或全身炎症知之甚少。此外，肥大细胞如何影响对纳米颗粒暴露的炎症反应尚不清楚。因此，我们比较了 C57BL/6 和 B6.Cg-Kit(W-sh) 肥大细胞缺陷小鼠在氧化铈纳米颗粒吸入后的肺部和心血管反应。C57BL/6 小鼠吸入氧化铈后表现出轻度肺部炎症。然而，B6.Cg-Kit(W-sh) 小鼠在吸入氧化铈后没有表现出类似程度的炎症。此外，C57BL/6 小鼠吸入氧化铈后，对腺苷的主动脉血管反应发生改变，并增加了心肌缺血/再灌注损伤，而 B6.Cg-Kit(W-sh) 小鼠则没有。体外氧化铈暴露导致培养的肥大细胞产生更多的 PGD₂、TNF-α、IL-6 和骨桥蛋白。这些发现表明，氧化铈纳米颗粒激活肥大细胞，导致肺部炎症、血管舒张功能障碍和心肌缺血/再灌注损伤加重。
