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 biopsi es from nine patients with systemic sclerosis and interstitial lung di sease, eight with 'lone' cryptogenic fibrosing alveolitis, two with cy stic fibrosis, two with extrinsic allergic alveolitis, two with Langer hans' 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 hyp erplastic type II pneumonocytes expressed intracellular TGF-beta(1). E xtracellular TGF-beta(1) was found in the fibrous tissue immediately b eneath the bronchial and hyperplastic alveolar epithelium. In normal l ung, however, the alveolar epithelium and alveolar interstitium were n egative 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 o f granulation tissue reacted strongly for the extracellular form of TG F-beta(1) and the overlying hyperplastic epithelium expressed the intr acellular form. In lymphangioleiomyomatosis, the ab errant smooth musc le cells strongly expressed intracellular TGF-beta(1) and the extracel lular form was expressed in the adjacent connective tissue. In giant c ell interstitial pneumonia, the numerous alveolar macrophages, includi ng the multinucleate forms, expressed intracellular TGF-beta(1), as di d 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-be ta(1) in hyperplastic type II pneumonocytes and the fibrosis underlyin g these cells suggests that TGF-beta(1) produced during alveolar epith elial regeneration may play a part in several forms of pulmonary fibro sis.