Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment.
Activin A is a homodimeric protein structurally and functionally related to transforming growth factor beta (TGF-beta), and the expression of activin A is modulated by TGF-beta. Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs. ICR mice were treated with BLM intraperitoneally for 10 days, whereas saline 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 using a polyclonal antibody to activin A revealed the presence of activin 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 and 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, suggesting that activin A may play a role in the pathogenesis of BLM-induced pulmonary fibrosis.
Matsuse
T
T
Department of Geriatrics and Pathology, Faculty of Medicine, University of Tokyo, Japan.
Fukuchi
Y
Y
Eto
Y
Y
Matsui
H
H
Hosoi
T
T
Oka
T
T
Ohga
E
E
Nagase
T
T
Orimo
H
H
D028341:Activins; D000818:Animals; D001681:Biological Assay; D001761:Bleomycin / Q000494:pharmacology*; D001980:Bronchi / Q000737:chemistry; D002478:Cells, Cultured; D004848:Epithelium / Q000737:chemistry; D005355:Fibrosis / Q000139:chemically induced; D006133:Growth Substances / Q000276:immunology / Q000302:isolation & purification*; D007150:Immunohistochemistry; D007265:Inhibins / Q000276:immunology / Q000302:isolation & purification*; D008168:Lung / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D013997:Time Factors; D014018:Tissue Distribution
D006133:Growth Substances; D028341:Activins; D001761:Bleomycin; D007265:Inhibins