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

Sarcoidosis is a chronic inflammatory disease of unknown cause charact erized by the formation of nonnecrotizing granulomas in affected tissu es, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming gro wth factor-beta(1) (TGF-beta(1)) is a potent cytokine that promotes fi brosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha(5) beta(1) fibronectin receptor. T he role of TGF-beta(1) in promoting lung fibrosis in the setting of pu lmonary sarcoidosis has not yet been investigated. Accordingly, we det ermined the extent and distribution of TGF-beta(1) in lung tissue obta ined from seven patients with clinical and histologic features of pulm onary sarcoidosis. The tissue distributions of TGF-beta(1), the TGF-be ta(1) binding proteoglycan decorin, fibronectin, and the alpha(5) beta (1) fibronectin receptor were assessed immunohistochemically. In all c ases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta(1). We further d emonstrated decorin, fibronectin, and the alpha(5) beta(1) fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue s urrounding the lesions. TGF-beta(1) staining was also observed in bron chiolar epithelial cells, hyperplastic Type II pneumocytes, and occasi onal alveolar macrophages. This study demonstrates enhanced tissue loc alization of TGF-beta(1) and related extracellular matrix proteins ass ociated with the nonnecrotizing granulomas of pulmonary sarcoidosis. T hrough its actions on matrix protein synthesis, TGF-beta(1) may modula te the fibrotic repair process accompanying granuloma healing in sarco idosis.