Mast cells contribute to altered vascular reactivity and ischemia-reperfusion injury following cerium oxide nanoparticle instillation.
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.
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Christopher J
CJ
Wingard
Dianne M
DM
Walters
Brook L
BL
Cathey
Susana C
SC
Hilderbrand
Pranita
P
Katwa
Sijie
S
Lin
Pu Chun
PC
Ke
Ramakrishna
R
Podila
Apparao
A
Rao
Robert M
RM
Lust
Jared M
JM
Brown
D000241:Adenosine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002563:Cerium / Q000633:toxicity*; D054405:Chemokine CCL3; D005786:Gene Expression Regulation / Q000187:drug effects; D006651:Histocytochemistry; D016753:Interleukin-10; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000737:chemistry; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction; D009206:Myocardium / Q000737:chemistry; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015230:Prostaglandin D2; D015427:Reperfusion Injury / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; C556062:IL10 protein, mouse; D018793:Interleukin-13; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D016753:Interleukin-10; D002563:Cerium; C030583:ceric oxide; D000241:Adenosine; D015230:Prostaglandin D2