Murine lung responses to ambient particulate matter: genomic analysis and influence on airway hyperresponsiveness.
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.
Wang
Ting
T
Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA.
Moreno-Vinasco
Liliana
L
Huang
Yong
Y
Lang
Gabriel D
GD
Linares
Jered D
JD
Goonewardena
Sascha N
SN
Grabavoy
Alayna
A
Samet
Jonathan M
JM
Geyh
Alison S
AS
Breysse
Patrick N
PN
Lussier
Yves A
YA
Natarajan
Viswanathan
V
Garcia
Joe G N
JG
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
D000393:Air Pollutants; D010047:Ovalbumin