title: Murine lung responses to ambient particulate matter: genomic analysis and influence on airway hyperresponsiveness.
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 mum) 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 (T(H)1) cytokines [interferon-gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha] and T(H)2 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Liliana
authors.initials: L
authors.lastname: Moreno-Vinasco
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Lang
authors.forename: Jered D
authors.initials: JD
authors.lastname: Linares
authors.forename: Sascha N
authors.initials: SN
authors.lastname: Goonewardena
authors.forename: Alayna
authors.initials: A
authors.lastname: Grabavoy
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Samet
authors.forename: Alison S
authors.initials: AS
authors.lastname: Geyh
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Breysse
authors.forename: Yves A
authors.initials: YA
authors.lastname: Lussier
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D023281:Genomics; D008168:Lung / Q000187:drug effects*; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage; D010316:Particle Size
chemical_list: D000393:Air Pollutants; D010047:Ovalbumin