To determine the role of IL-5 in airway remodeling, IL-5–deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5–deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, α-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-β. In contrast, IL-5–deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-β, suggesting that eosinophils are a significant source of TGF-β in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial αVβ6 integrin expression, as well as significantly higher levels of bioactive lung TGF-β in WT compared with IL-5–deficient mice. Increased airway epithelial expression of αVβ6 integrin may contribute to the increased activation of latent TGF-β. These results suggest an important role for IL-5, eosinophils, αVβ6, and TGF-β in airway remodeling.
Jae Youn Cho, Marina Miller, Kwang Je Baek, Ji Won Han, Jyothi Nayar, Sook Young Lee, Kirsti McElwain, Shauna McElwain, Stephanie Friedman, David H. Broide