Immunolocalization of transforming growth factor alpha and epidermal growth factor receptor in lungs of patients with cystic fibrosis

Transforming growth factor alpha (TGF-alpha) is expressed in respiratory ep ithelial cells and alveolar macrophages during development and following lu ng injury. In the present study, the presence and sites of synthesis of TGF -alpha and its receptor, the epidermal growth factor receptor (EGF-R), were assessed in lung tissue from patients with severe lung disease caused by c ystic fibrosis (CF). Lung sections from 24 individuals with CF, obtained at the time of lung transplantation, were compared to lung sections from five lung donors without CE Cellular sites of TGF-alpha EGF-R, and cellular sit es of proliferation were assessed by immunohistochemistry. All CF lung sect ions contained multiple cell types with detectable TGF-alpha. Compared to c ontrol sections, intensity of TGF-alpha immunostaining in macrophages, airw ay epithelial cells, and peribronchial submucosal cells was increased. EGF- R was detected in respiratory epithelial and peribronchial stromal cells bu t not in alveolar macrophages. The intensity of EGF-R staining in CF lung t issue did not differ from that of controls. An increased number of cells ex pressing Ki-67 nuclear antigen was detected in peribronchial submucosal cel ls but not bronchiolar epithelial cells in the CF lungs. The increased expr ession of TGF-alpha in CF lung tissue supports the concept that TGF-alpha p lays a role in paracrine/autocrine regulation of lung remodeling associated with injury and repair in the lungs of individuals with cystic fibrosis.