TGF-β Signaling Pathways in Different Compartments of the Lower Airways of Patients With Stable COPD

BACKGROUND: The expression and localization of transforming growth factor-beta (TGF-beta) pathway proteins in different compartments of the lower airways of patients with stable COPD is unclear. We aimed to determine TGF-beta pathway protein expression in patients with stable COPD. METHODS: The expression and localization of TGF-beta pathway components was measured in the bronchial mucosa and peripheral lungs of patients with stable COPD (n = 44), control smokers with normal lung function (n = 24), and control nonsmoking subjects (n = 11) using immunohistochemical analysis. RESULTS: TGF-beta 1, TGF-beta 3, and connective tissue growth factor expression were significantly decreased in the bronchiolar epithelium, with TGF-beta 1 also decreased in alveolar macrophages, in patients with stable COPD compared with control smokers with normal lung function. TGF-beta 3 expression was increased in the bronchial lamina propria of both control smokers with normal lung function and smokers with mild/moderate stable COPD compared with control nonsmokers and correlated significantly with pack-years of smoking. However, TGF-beta 3(+) cells decreased in patients with severe/very severe COPD compared with control smokers. Latent TGF-beta binding protein 1 expression was increased in the bronchial lamina propria in subjects with stable COPD of all severities compared with control smokers with normal lung function. Bone morphogenetic protein and activin membrane-bound inhibitor expression (BAMBI) in the bronchial mucosa was significantly increased in patients with stable COPD of all severities compared with control subjects. No other significant differences were observed between groups for all the other molecules studied in the bronchial mucosa and peripheral lung. CONCLUSIONS: Expression of TGF-beta s and their regulatory proteins is distinct within different lower airway compartments in stable COPD. Selective reduction in TGF-beta 1 and enhanced BAMBI expression may be associated with the increase in autoimmunity in COPD.