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Comparative inflammatory effects of differential particulate matter species in an OVA-sensitization and challenge model
Citation:
Williams, M., M. Daniels, E. Boykin, T. Smith, N. Coates, L. Copeland, D. Andrews, J. Richards, AND Ian Gilmour. Comparative inflammatory effects of differential particulate matter species in an OVA-sensitization and challenge model. Presented at The Society of Toxicology, March 10 - 14, 2013.
Impact/Purpose:
Acute exposure to ambient particulate matter (APM) provokes immunological activation in the lung, inflammatory and pro-oxidative responses that collectively resemble allergic asthma in humans. Environmental APM, environmental diesel exhaust particles (eDEP) and emission source DEP (cDEP) may differentially provoke an allergic inflammatory response. We have tested this hypothesis in a physiologically relevant animal model to advance our mechanistic understanding of the immune adjuvant-promoting effects of respirable particulate matter in the environment.
Description:
Exposure to respirable ambient particulate matter (APM) provokes allergic immunity that may also occur on exposure to environmental diesel exhaust particles (eDEP) or emission source DEP (cDEP). Our hypothesis tested whether APM, eDEP or cDEP provide immune adjuvancy in an antigen (ovalbumin, OVA) sensitization and challenge model. We assayed for oxidative stress, inflammatory and cytokine analytes in BALF,assay of lung infiltrating cells, assay of serological analytes (total IgE, IgG1, IgG2a), and antigen-specific recall responses of primary lymph node cells (pLNC). All PM species increased markers of airway or allergic inflammation. However, eDEP or cDEP sensitized mice had lower levels of superoxide dismutase as compared APM, with no effect other oxidative stress markers (p<0.005). By contrast, all PM species enhanced eosinophil and neutrophil infiltration to the lung as compared saline or OVA alone (p<0.001). These effects for APM (p<0.005) and cDEP (p<0.05) were concordant with enhanced levels of pro-Th2 cytokines like IL-5 in BALF. Assay of isotype class-switching was less informative. All PM species partially augmented total IgE as compared saline, but not LPS control or each other, and dampened secretion of IgG2a (p=0.07) and IgG1 (p=0.059) as compared low-dose LPS/OVA. In OVA-specific recall responses, pLNC proliferation was enhanced in mice sensitized with eDEP and particularly cDEP, which provoked robust IL-5 and IL-13 secretion (p<0.01). We conclude that all PM species provoked airway and allergic inflammation. However diesel PM, and particularly cDEP were most effective in sensitizing mice and driving Th2-type cytokine and OVA-specific responses ex vivo. This study further demonstrates that respirable PM differentially provoke allergic inflammation, and provides new insights on signaling changes contributing to these effects. This abstract does not reflect US EPA policy.