Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine / pharmacology
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Analysis of Variance
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Animals
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / physiology
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Bronchoalveolar Lavage Fluid / cytology
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Cerium / toxicity*
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Chemokine CCL3
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Gene Expression Regulation / drug effects
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Histocytochemistry
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Interleukin-10
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Interleukin-13 / genetics
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Interleukin-13 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lung / chemistry
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Male
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Mast Cells / metabolism*
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Mast Cells / pathology
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Metal Nanoparticles / chemistry
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Metal Nanoparticles / toxicity*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myocardial Infarction
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Myocardium / chemistry
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Osteopontin / genetics
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Osteopontin / metabolism
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Particle Size
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Pneumonia / chemically induced
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Pneumonia / metabolism
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Pneumonia / pathology
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Prostaglandin D2
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Reperfusion Injury / metabolism*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Ccl3 protein, mouse
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Chemokine CCL3
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IL10 protein, mouse
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Interleukin-13
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Interleukin-6
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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Osteopontin
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Interleukin-10
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Cerium
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ceric oxide
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Adenosine
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Prostaglandin D2