Murine lung response to ambient particulate matter: Genomic analysis and influence on airway hyperresponsiveness

Ting Wang, Liliana Moreno-Vinasco, Yong Huang, Gabriel D. Lang, Jered D. Linares, Sascha N. Goonewardena, Alayna Grabavoy, Jonathan M. Samet, Alison S. Geyh, Patrick N. Breysse, Yves A. Lussier, Viswanathan Natarajan, Joe G.N. Garcia

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Background: Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma prevalence and exacerbations. Objective: We investigated pathophysiologic responses to Baltimore, Maryland, ambient PM (median diameter, 1.78 μm) in a murine model of asthma and attempted to identify PM-specific genomic/molecular signatures. Methods: We exposed ovalbumin (OVA)-sensitized A/J mice intratracheally to PM (20 mg/kg), and assayed both AHR and bronchoalveolar lavage (BAL) on days 1, 4, and 7 after PM exposure. Lung gene expression profiling was analyzed in OVA- and PM-challenged mice. Results: Consistent with this murine model of asthma, we observed significant increases in airway responsiveness in OVA-treated mice, with PM exposure inducing significant changes in AHR in both naive mice and OVA-induced asthmatic mice. PM evoked eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of type 1 T helper (TH1) cytokines [interferon-γ, interleukin-6 (IL-6), tumor necrosis factor-α] and TH2 cytokines (IL-4, IL-5, eotaxin) into murine airways. Furthermore, PM consistently induced expression of genes involved in innate immune responses, chemotaxis, and complement system pathways. Conclusion: This study is consistent with emerging epidemiologic evidence and indicates that PM exposure evokes proinflammatory and allergic molecular signatures that may directly contribute to the asthma susceptibility in naive subjects and increased severity in affected asthmatics.

Original languageEnglish
Pages (from-to)1500-1508
Number of pages9
JournalEnvironmental Health Perspectives
Volume116
Issue number11
DOIs
StatePublished - 2008

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • Intelectin
  • Particulate matter
  • Toxicogenomics

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