EPITHELIAL CELL-DERIVED TRANSFORMING GROWTH-FACTOR-BETA IN BLEOMYCIN-INDUCED PULMONARY INJURY

We have investigated whether enhanced secretion of transforming growth factor-beta (TGF-beta) by distal respiratory epithelial cells was ass ociated with the development of bleomycin-induced pulmonary fibrosis. Type 2 pneumocyte-enriched preparations of bronchioloalveolar epitheli al cells from normal mouse lung tissue released latent TGF-beta when c ultured in serum-free medium. TGF-beta in culture supernatants could b e detected using a sensitive enzyme immunoassay which employed enzyme complex amplification as a reporter system, as well as by a radiolabel led receptor competition assay. Exposure to bleomycin and other potent ially fibrogenic stimuli in vitro did not stimulate production of TGF- beta by the epithelial cells but release was enhanced by treatment of the cells with interferon-gamma. Type 2 pneumocyte-enriched cell prepa rations obtained following induction of a pulmonary inflammatory respo nse by administration of intratracheal bleomycin to susceptible C57BL/ 6 mice did not demonstrate increased release of TGF-beta in culture. H owever, the concentration of TGF-beta in bronchoalveolar lavage (BAL) fluids was significantly elevated compared to controls at 1 and 2 week s after bleomycin-induced injury in these mice. No such increase was d etected in BAL fluids from BALB/c mice, which are resistant to the eff ects of bleomycin. These results provide no support for a pathogenetic role of alveolar epithelial cell-derived TGF-beta in bleomycin-induce d pulmonary fibrosis. Nevertheless, elevated levels of TGF-beta in BAL fluids may provide a marker of the progression of pulmonary injury to fibrosis.