Maturational Changes in Airway Remodeling after Chronic Exposure to Ovalbumin in Sensitized Guinea Pigs: Role of Cell Renewal of Airway Resident Cells

摘要

We wanted to know whether airway remodeling caused by chronic exposures to antigen differed depending on the degree of maturation of animals. We sensitized guinea pigs at different stages of maturation: juvenile (approximately 200 g in body weight), adult (400 g), and old animals (800 g). Then, animals were repeatedly challenged with inhaled ovalbumin (0.3% or 3%) or vehicle twice a week for 6 wk. After the final challenge, the lungs were excised for the histologic evaluation of changes in the thickness of the inner wall area (Ti), the smooth muscle area (Tm), and the outer wall area (To) in noncartilaginous airway dimensions. To clarify whether or not the observed changes were due to renewal of airway cells, we stained the samples with labeled nucleotide 5′-bromo-2′-deoxyuridine (BrdU), which we injected repeatedly during the challenge periods. Chronic exposures to antigen induced airway wall thickening regardless of their stages of maturation. However, prominent areas of thickening differed between the three groups. Ti increased more remarkably in juvenile and adult animals than in old ones. By contrast, Tm significantly increased only in old animals. BrdU staining revealed more renewal of epithelial cells in juvenile and adult animals than in old ones (juvenile adult > old), suggesting that increased renewal of epithelial cells contributed to the thickening of Ti in juvenile and adult animals. By contrast, only a slight increase in smooth muscle cell renewal was found even in old animals, indicating that an increase in Tm was due to factors such as hypertrophy. These results show that the development of antigen-induced airway remodeling is partly modified by the degree of maturation of animals in vivo.Abbreviations: BrdU, 5′-bromo-2′-deoxyuridine; HSA, human serum albumin; OA, ovalbumin; Pi, internal perimeter; Ti, the thickness of the inner wall area; Tm, the thickness of smooth muscle; To, the thickness of the outer wall area