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Differential and Dose-Dependent Inflammatory Responses in a Mouse Model of Respirable Instillation of Environmental Diesel, Emission-Source Diesel , Emmission-Source Diesel and Ambient Air Pollution Particles In Vivo.
Citation:
WILLIAMS, M. A., M. J. DANIELS, E. BOYKIN, L. B. COPELAND, AND M. I. GILMOUR. Differential and Dose-Dependent Inflammatory Responses in a Mouse Model of Respirable Instillation of Environmental Diesel, Emission-Source Diesel , Emmission-Source Diesel and Ambient Air Pollution Particles In Vivo. Presented at American Thoracic Society (ATS) Meeting, Denver, CO, May 13 - 18, 2011.
Impact/Purpose:
Acute single exposures to ambient airborne, environmental diesel and emission-source diesel particulate matter (PM) instruct rapid dose-dependent pulmonary inflammation in a mouse model naive to prior PM exposure. These studies provide detail of hte optimal doses of PM species in protocols designed to test immune adjuvancy of PM species
Description:
Rationale: Previously, we found that ambient particulate matter (APM) activates pulmonary dendritic cells in vitro. We hypothesized that single acute exposures to PM would promote inflammatory activation of the lung in vivo and provide information on early immunological events of PM exposure. We report on a comparative time-and dose-dependent study following instillation of APM, environmental diesel PM (E-DEP) and emission-source compressor diesel PM (C-DEP) in a mouse model naive to prior PM exposure. Methods: Female C57BI/6J mice aged 10-12 weeks, were exposed to APM, E-DEP or C-DEP for 4h or 24h at 0, 10,25, and 50ug in 50ul 0.9% w/v saline by oropharyngeal delivery (n=6 per group, n=144 total). We measured a panel of markers in the bronchoalveolar fluid (BALF) including total protein, lactate dehydrogenase (LDH), microalbumin (MIA), gamma glutamyl transferase (GGT), N-acetyl-ß-D-glucosaminidase (NAG), differential cytology of inflammatory cell infiltrates and quantitation of CXCL1 (KC -a neutrophilic chemokine important in inflammation) and thymic stromal Iymphopoietin (TSLP -a cytokine that modulates antigen presenting cells to direct Th2-like responses by CD4+ T cells) in cell-free BALF by ELISA platforms. Results: While none of the PM species altered release of GGT or NAG, LDH and total protein were dose-dependently enhanced by 24h in mice exposed to APM or E-DEP while only at the highest dose of 50ug did C DEP drive enhanced LDH and protein release in BALF. Release of MIA was weakly induced by all PM species. While the major cellular type in BALF were macrophages, significant and rapid (within 4h following instillation) dose-dependent neutrophil infiltration was seen with all PM species. Remarkably both APM and E-DEP and to a lesser degree C-DEP provoked eosinophilic infiltration at both 4h and 24h post-instillation. Consistent with neutrophilic infiltration, we noted dose-and time-dependent release of CXCL 1 in the BALF in response to APM, E-DEP, and to a lesser degree C-DEP. While TSLP release was detected in the BALF in control mice, it was largely unaffected by PM instillation in this model. Conclusions: Instillation of all PM species provoked dose-and time-dependent inflammation in the lung as measured by neutrophil infiltration, enhanced secretion of CXCL1 and biochemical markers present in the BALF. These studies provide evidence not only of the inflammatory properties of source specific PM species but experimental detail of the optimal doses of PM species in antigen sensitization and challenge protocols designed to test the immune adjuvancy potential of those PM species. (This abstract does not reflect EPA policy).