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 epithelial cell deoxyribonucleic acid (DNA) synthesis, cell recruitment and airway 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 with the DNA S-phase marker bromodeoxyuridine (BrdU). Using a triple immunohistochemical staining technique, BrdU incorporation into ASM and epithelium was quantified employing 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 epithelium, from 1.3 (95% CI 0.6-2.0) BrdU-positive cells x mm basement membrane(-1) in 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 airways. Increased rates of deoxyribonucleic acid synthesis in both airway smooth muscle and epithelial cells along with changes to the airway wall pathology may precede the establishment of smooth muscle thickening and airway remodelling after repeated allergen exposure in rats. This model seems to be appropriate for studying structural changes within the airways as observed in asthma.
Salmon
M
M
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Walsh
D A
DA
Koto
H
H
Barnes
P J
PJ
Chung
K F
KF
D000199:Actins / Q000378:metabolism; D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001798:Blood Proteins / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018801:CD2 Antigens / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004195:Disease Models, Animal; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D010047:Ovalbumin / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D012260:Ribonucleases; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D000199:Actins; D000485:Allergens; D001798:Blood Proteins; D018801:CD2 Antigens; D047091:Eosinophil Granule Proteins; D010047:Ovalbumin; D004247:DNA; D012260:Ribonucleases; D001973:Bromodeoxyuridine