IMMUNOHISTOCHEMICAL LOCALIZATION OF TRANSFORMING GROWTH FACTOR-BETA(1) IN THE NONNECROTIZING GRANULOMAS OF PULMONARY SARCOIDOSIS

Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by the formation of nonnecrotizing granulomas in affected tissues, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming growth factor-beta(1) (TGF-beta(1)) is a potent cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha(5) beta(1) fibronectin receptor. The role of TGF-beta(1) in promoting lung fibrosis in the setting of pulmonary sarcoidosis has not yet been investigated. Accordingly, we determined the extent and distribution of TGF-beta(1) in lung tissue obtained from seven patients with clinical and histologic features of pulmonary sarcoidosis. The tissue distributions of TGF-beta(1), the TGF-beta(1) binding proteoglycan decorin, fibronectin, and the alpha(5) beta(1) fibronectin receptor were assessed immunohistochemically. In all cases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta(1). We further demonstrated decorin, fibronectin, and the alpha(5) beta(1) fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue surrounding the lesions. TGF-beta(1) staining was also observed in bronchiolar epithelial cells, hyperplastic Type II pneumocytes, and occasional alveolar macrophages. This study demonstrates enhanced tissue localization of TGF-beta(1) and related extracellular matrix proteins associated with the nonnecrotizing granulomas of pulmonary sarcoidosis. Through its actions on matrix protein synthesis, TGF-beta(1) may modulate the fibrotic repair process accompanying granuloma healing in sarcoidosis.