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Mast cells contribute to alterations in vascular reactivity and exacerbation of ischemia reperfusion injury following ultrafine PM exposure
Citation:
Wingard, C. J., R. M. Lust, D. Walters, R. B. DEVLIN, W. CASCIO, AND J. M. Brown. Mast cells contribute to alterations in vascular reactivity and exacerbation of ischemia reperfusion injury following ultrafine PM exposure. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
The aim of this study was to examine the activation of mast cells in the pulmonary and cardiovascular pathology after exposure to UFPM.
Description:
Increased ambient fine particulate matter (FPM) concentrations are associated with increased risk for short-term and long-term adverse cardiovascular events. Ultrafine PM (UFPM) due to its size and increased surface area might be particularly toxic. Mast cells are well recognized for their prominent role in allergic inflammation, asthma, and cardiovascular disease, yet their role in cellular response to exposure to PM is unknown The aim of this study was to examine the activation of mast cells in the pulmonary and cardiovascular pathology after exposure to UFPM. Murine bone marrow-derived mast cells were exposed in vitro to UFPM and both IgE and non-IgE mediated mast cell activation was examined. Additionally, we assessed pulmonary inflammation, aortic vascular reactivity, and myocardial ischemia/reperfusion (IR) injury in UFPM instilled C57Bl/6 and B6.Cg_Kitw-sh mast cell deficient mice. Mast cells did not degranulate after in vitro exposure to UFPM in the absence of IgE. Yet, UFPM exposure accentuated IgE-mediated degranulation and promoted cytokine production. In vivo studies revealed that mice exposed to UFPM exhibited increased pulmonary inflammation. Further, UFPM instilled C57Bl/6 mice exhibited increased myocardial IR infarct size by ~40% while B6.Cg_Kitw-sh mice displayed only a ~15% expansion. Lastly, C57Bl/6 mice exposed to UFPM exhibited decreased vascular constriction to norepinephrine that was largely absent in B6.Cgsh KitW-mice. These findings demonstrate that UFPM can direct mast cell production of proinflammatory cytokines which may contribute to myocardial infarct, altered vascular reactivity and adverse health effects in vivo. This abstract does not necessarily reflect EPA policy. Supported in part by grants from the Phillip Morris USA and International Research Program, NIH ROIES5016246 and East Carolina University.