Mast cells contribute to altered vascular reactivity and ischemia-reperfusion injury following cerium oxide nanoparticle instillation

作者：Wingard Christopher J; Walters Dianne M; Cathey Brook L; Hilderbrand Susana C; Katwa Pranita; Lin Sijie; Ke Pu Chun; Podila Ramakrishna; Rao Apparao; Lust Robert M; Brown Jared M^*

来源：Nanotoxicology, 2011, 5(4): 531-545.

DOI：10.3109/17435390.2010.530004

• Mast cell
• mast cell deficient mice
• osteopontin
• sash mice
• ischemia-reperfusion injury

Cerium oxide (CeO(2)) represents an important nanomaterial with wide ranging applications. However, little is known regarding how CeO(2) 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 CeO(2) nanoparticle instillation. C57BL/6 mice instilled with CeO(2) exhibited mild pulmonary inflammation. However, B6.Cg-Kit(W-sh) mice did not display a similar degree of inflammation following CeO(2) instillation. Moreover, C57BL/6 mice instilled with CeO(2) 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 CeO(2) exposure resulted in increased production of PGD(2), TNF-alpha, IL-6 and osteopontin by cultured mast cells. These findings demonstrate that CeO(2) nanoparticles activate mast cells contributing to pulmonary inflammation, impairment of vascular relaxation and exacerbation of myocardial ischemia/reperfusion injury.

• 出版日期2011-12