IMMUNOHISTOCHEMICAL LOCALIZATION OF TRANSFORMING GROWTH FACTOR-BETA(1) IN THE LUNGS OF PATIENTS WITH SYSTEMIC-SCLEROSIS, CRYPTOGENIC FIBROSING ALVEOLITIS AND OTHER LUNG DISORDERS

To study the role of transforming growth factor-beta(1) (TGF-beta(1)) in the pathogenesis of pulmonary fibrosis we have examined lung biopsies from nine patients with systemic sclerosis and interstitial lung disease, eight with 'lone' cryptogenic fibrosing alveolitis, two with cystic fibrosis, two with extrinsic allergic alveolitis, two with Langerhans' cell histiocytosis, one with lymphangioleiomyomatosis, one with giant cell interstitial pneumonia, and one adenocarcinoma of the lung. In cryptogenic fibrosing alveolitis, both 'lone' and associated with systemic sclerosis, alveolar macrophages, bronchial epithelium and hyperplastic type II pneumonocytes expressed intracellular TGF-beta(1). Extracellular TGF-beta(1) was found in the fibrous tissue immediately beneath the bronchial and hyperplastic alveolar epithelium. In normal lung, however, the alveolar epithelium and alveolar interstitium were negative for both forms of TGF-beta(1). There was strong expression of TGF-beta(1) in hyperplastic mesothelium and its underlying connective tissue and in Langerhans' cells in the two cases of histiocytosis. In the organizing pneumonia in cystic fibrosis, the intra-alveolar buds of granulation tissue reacted strongly for the extracellular form of TGF-beta(1) and the overlying hyperplastic epithelium expressed the intracellular form. In lymphangioleiomyomatosis, the ab errant smooth muscle cells strongly expressed intracellular TGF-beta(1) and the extracellular form was expressed in the adjacent connective tissue. In giant cell interstitial pneumonia, the numerous alveolar macrophages, including the multinucleate forms, expressed intracellular TGF-beta(1), as did the hyperplastic alveolar epithelium. Adenocarcinoma cells expressed the intracellular form of TGF-beta(1) strongly and the extracellular form was evident in the tumour stroma. The strong expression of TGF-beta(1) in hyperplastic type II pneumonocytes and the fibrosis underlying these cells suggests that TGF-beta(1) produced during alveolar epithelial regeneration may play a part in several forms of pulmonary fibrosis.