Citation:

WILLIAMS, M. A., M. J. DANIELS, E. BOYKIN, L. B. COPELAND, J. R. LEHMANN, J. E. RICHARDS, AND M. I. GILMOUR. Immunotoxicological Analysis of the Immune Adjuvant Effects of Source Specific Diesel and Environmental Ambient Particulate Matter in a Murine Sensitization And Challenge Model. Presented at American Thoracic Society (ATS) Annual Meeting, San Francisco, CA, May 18 - 23, 2012.

Impact/Purpose:

Airborne pollutants are thought to behave as immunological adjuvants that may exacerbate pre-existing disease or provoke induction of disease like asthma following exposure ofthe lung to infectious agents like respiratory viruses. Exposing mice to PM differentially sensitized them to OVA with the greatest immune adjuvancy effects seen for APM and eDEP. While APM and eDEP provoked dramatic Th2associated cytokine responses and OVA-specific recall responses ex vivo, all PM species were equally effective at IgE class switching. This study supports an increasing appreciation that respirable PM species rna rovoke aller ic inflammato airwa s disease like asthma.

Description:

Rationale: Acute exposure to ambient particulate matter (APM) provokes oxidative and inflammatory lung activation in vivo. Here, we test the hypothesis that environmental diesel exhaust particles (eDEP), emission source-specific DEP (cDEP) and APM differentially provoke an allergic immune response in an animal model assessing the immune adjuvancy of PM species. Methods: We assessed pulmonary function, lung pathology (hematoxylin/eosin; trichrome histochemistry), biochemical and immunological effects (multiplex cytokine array; antigen recall and cell proliferation assays of regional lymph node cells (LNC) following oropharyngeal instillation of PM to C57BI/6J mice in an ovalbumin (OVA) immune sensitization and challenge model. Mice (n=6 per group) were sensitized to PM with/without OVA on days (d) 0,1,3,6 then challenged with OVA d 13,14,20,21 and endpoints measured on d22, d23. Controls included sham-exposed mice (saline alone), OVA alone or endotoxin (LPS) sensitized, OVA challenged mice. Results: Pulmonary function as measured by whole body plethysmography was unaffected by sensitization and challenge exposures in this model. While all PM species provoked increases in markers associated with airway inflammation and immunotoxicity, mice sensitized and challenged with APM and OVA provoked greater levels of gammaglutamyl transferase (GGT) and N -acetylglucosaminidase (NAG) in BAL fluid as compared eDEP or cDEP (P<0.05). By contrast, all PM species induced marked infiltration of eosinophils and neutrophils to the lung as compared mice sham exposed to saline or OVA alone (P<0.02). These effects were associated with enhanced IL-5 and KC secretion-cytokines that activate eosinophils and neutrophils respectively in allergic inflammatory responses. Evidence for an immune adjuvant role for PM in vivo was seen in primary cultures of peribronchial LNC that displayed both enhanced OVA-specific proliferation and Th2-mediated allergic inflammatory cytokine responses ex vivo. The greatest LNC proliferation was seen in mice sensitized to OVA in the presence of APM and eDEP as compared to mice exposed to saline or OVA alone (P<0.01) -an observation associated with enhanced secretion of IL-4, IL-5 and IL-13 in LNC cultures and serological class switching to IgE (P<0.05). Conclusions: Exposing mice to PM differentially sensitized them to OVA with the greatest immune adjuvancy effects seen for APM and eDEP. While APM and eDEP provoked dramatic Th2-associated cytokine responses and OVA-specific recall responses ex vivo, all PM species were equally effective at IgE class switching. This study supports an increasing appreciation that respirable PM species may provoke allergic inflammatory airways disease and provides new insights on signaling changes contributing to these effects. This abstract does not reflect US -EPA policy.

Record Details:

Planning Links: