EXPRESSION OF IMMUNOREACTIVE AND BIOACTIVE ACTIVIN-A PROTEIN IN ADULTMURINE LUNG AFTER BLEOMYCIN TREATMENT

Activin A is a homodimeric protein structurally and functionally relat ed to transforming growth factor beta (TGF-beta), and the expression o f activin A is modulated by TGF-beta. Here, we demonstrate the express ion of activin A in normal and bleomycin (BLM)-treated murine lungs. I CR mice were treated with BLM intraperitoneally for 10 days, whereas s aline vehicle was injected into control mice. Intra-alveolar fibrotic changes were observed in the lung tissue obtained from the mice at day 14 after the final BLM administration. Immunohistochemical studies us ing a polyclonal antibody to activin A revealed the presence of activi n A in the bronchiolar epithelium and smooth muscle cells of veins in both control and BLM-treated mice. In the BLM-treated mice at days 7 a nd 14, the marked infiltration of immunoreactive alveolar macrophages was observed in the area of fibrotic changes. Bioactivity of activin A measured by erythroid differentiation factor assay in the conditioned medium of alveolar macrophages obtained from BLM-treated mice at day 14 was significantly increased. These findings indicate that alveolar macrophages are a potent source of activin A after BLM treatment. The present study demonstrates for the first time the abundant expression of activin A in murine lung tissues after BLM administration, suggesti ng that activin A may play a role in the pathogenesis of BLM-induced p ulmonary fibrosis.