Airway Asthmatic Inflammation and Asthma Gene Dysregulation by Airborne Particulate Matter in Phoenix AZ and Sacramento CA: A Comparison Study
Ting Wang (1), Liliana Moreno-Vinasco (1), Lyndsay Joson (1), Gabriel D. Lang (1), Jonathan M. Samet (2), Ana M. Rule (3), Juan P. Ramos-Bonilla (3), Jana N. Mihalic (3), Lisa Polyak (3), Alison S Geyh (3), Patrick N Breysse (3), Viswanathan Natarajan (1), Joe G. N. Garcia (1)
(1) University of Chicago, Chicago, (2) University of Southern California, Los Angeles, (3) Johns Hopkins University, Baltimore
Abstract Number: 350
Preference: Poster Presentation
Last modified: November 9, 2009
Working Group: sq5
BACKGROUND: Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiological studies have demonstrated that exposure to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma exacerbations. OBJECTIVES: In a murine model of asthma, we compared pathophysiological alterations and PM-specific asthmatic gene dysregulation in response to ambient fine PM (0.1-3.0 Ám) collected using a high volume cyclone system from Phoenix, AZ (PHX) and Sacramento, CA (SAC), two cities with differential cardiopulmonary morbidity association with ambient PM. METHODS: Ovalbumin (OVA)-sensitized and challenged A/J mice were exposed to PM (1-10 mg/kg, intratracheal instillation). Both airway hyperresponsiveness (AHR) and bronchoalveolar lavage (BAL) were analyzed 4 days post PM exposure. Lung gene expression profiling was analyzed by real-time PCR. RESULTS: Each PM types (PHX, SAC, and SRM1648a as a positive control) promoted AHR, evoked eosinophil and neutrophil infiltration into airways, and elevated BAL protein content. Furthermore, PM consistently induced expressions of asthmatic genes: Cxcl2, Clca3, Tff2, Muc5b, Cfb, EAR11. PHX PM exhibited more severe dysregulation with marked increases in AHR (1.34 fold increase compared to SAC PM, p<0.05) and BAL inflammatory leukocytes infiltration (1.31 fold increase compared to SAC PM, p<0.05) and dysregulated asthmatic genes (p<0.05 compared to SAC PM), including Cxcl2 (1.61 fold), Cfb (1.29 fold), EAR11 (2.32 fold). CONCLUSION: These studies are consistent with rodent and human data which suggest PM exposure evokes pro-inflammatory and allergic molecular signatures which may directly exacerbate asthma severity. Further composition analysis of PM from PHX and SAC may reveal the etiology of the significant differential effects of these PM in triggering pathophysiological and genomic parameters. These studies were supported by Environmental Protection Agency/Johns Hopkins Particulate Matter Research Center Grant #RD83241701.