Airway fibrosis in a mouse model of airway inflammation.
BALB/c mice were sensitized to ovalbumin by systemic injection and then exposed for up to 8 weeks to ovalbumin aerosols in whole body chambers. A pattern of airway inflammation, mucous cell hypertrophy and hyperplasia, and airway remodeling with submucosal fibrosis was observed as lesions evolved over time. Larger conducting airways were removed from the lungs by microdissection. Airway fibrosis was quantified by direct assay for collagen content, which was significantly increased after 4 and 8 weeks of exposure to ovalbumin aerosol. Based upon PCR analysis of mRNA levels in the airways, most of the newly synthesized collagen was Type I. Relaxin, administered by continuous infusion over the second half of a 4-week exposure to ovalbumin, was able to inhibit the accumulation of collagen in the airways of exposed mice. Thus, stimulation of collagen degradation by an activator of collagen breakdown by matrix metalloproteinases appears to be an effective therapeutic strategy in prevention of airway fibrosis in this animal model. Whole body plethysmography of unrestrained mice indicated functional changes in airway reactivity in the lungs of exposed animals occurring in conjunction with the reported structural changes. This result indicates that the ovalbumin-exposed mouse may be a suitable model for examining structure-function relationships in the lungs of animals with a predictable time course of airway inflammation, remodeling, and fibrosis and for testing potential new drugs for treatment of asthma or chronic bronchitis at a mechanistic level.
Kenyon
Nicholas J
NJ
Pulmonary/Critical Care Medicine, School of Medicine, University of California, Davis, CA 95616, USA.
Ward
Rachel W
RW
Last
Jerold A
JA
D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D012065:Relaxin / Q000494:pharmacology
D000336:Aerosols; D012333:RNA, Messenger; D012065:Relaxin; D010047:Ovalbumin; D003094:Collagen