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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: 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

Published In Nanotoxicology, (2011 Dec)

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

PubMed ID: 21043986 Exiting the NIEHS site

MeSH Terms: Adenosine/pharmacology; Analysis of Variance; Animals; Aorta, Thoracic/drug effects; Aorta, Thoracic/physiology; Bronchoalveolar Lavage Fluid/cytology; Cerium/toxicity*; Chemokine CCL3; Gene Expression Regulation/drug effects; Histocytochemistry; Interleukin-10; Interleukin-13/genetics; Interleukin-13/metabolism; Interleukin-6/genetics; Interleukin-6/metabolism; Lung/chemistry; Male; Mast Cells/metabolism*; Mast Cells/pathology; Metal Nanoparticles/chemistry; Metal Nanoparticles/toxicity*; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardium/chemistry; Osteopontin/genetics; Osteopontin/metabolism; Particle Size; Pneumonia/chemically induced; Pneumonia/metabolism; Pneumonia/pathology; Prostaglandin D2; Reperfusion Injury/metabolism*; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/metabolism; Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/metabolism

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