Repeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synthesis and remodelling

Chronic inflammation in asthmatic airways can lead to characteristic airway smooth muscle (ASM) thickening and pathological changes within the airway wall. This study assessed the effect of repeated allergen exposure on ASM and epi thelial cell deoxyribonucleic acid (DNA) synthesis, cell recruitment and ai rway wall pathology. Brown-Norway rats were sensitized and then exposed to ovalbumin or saline aerosol every 3 days on six occasions. After the final exposure, rats were administered twice daily for 7 days,vith the DNA S-phas e marker bromodeoxyuridine (BrdU). Using a triple immunohistochemical stain ing technique, BrdU incorporation into ASM and epithelium was quantified em ploying computer-assisted image analysis. There were >3-fold mean increases in BrdU incorporation into ASM from 1.3% of cells (95% confidence interval (CI) 1.0-1.6) in saline controls to 4.7% (95% CI 2.6-6.7) after allergen exposure (p<0.001), and in airway epitheliu m, from 1.3 (95% CI 0.6-2.0) BrdU-positive cells mm basement membrane(-1) i n saline controls to 4.9 (95% CI 3.0-6.7) after allergen exposure (p<0.001) . There was increased subepithelial collagen deposition and mucus secretion along with a significant eosinophil and lymphocyte recruitment to the airw ays. Increased rates of deoxyribonucleic acid synthesis in both airway smooth mu scle and epithelial cells along with changes to the airway wall pathology m ay precede the establishment of smooth muscle thickening and airway remodel ling after repeated allergen exposure in rats. This model seems to be appro priate for studying structural changes within the airways as observed in as thma.