Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment

Am J Respir Cell Mol Biol. 1995 Jul;13(1):17-24. doi: 10.1165/ajrcmb.13.1.7541220.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins
  • Animals
  • Biological Assay
  • Bleomycin / pharmacology*
  • Bronchi / chemistry
  • Cells, Cultured
  • Epithelium / chemistry
  • Fibrosis / chemically induced
  • Growth Substances / immunology
  • Growth Substances / isolation & purification*
  • Immunohistochemistry
  • Inhibins / immunology
  • Inhibins / isolation & purification*
  • Lung / chemistry*
  • Lung / cytology
  • Lung / drug effects
  • Macrophages, Alveolar / chemistry
  • Macrophages, Alveolar / cytology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle, Smooth, Vascular / chemistry
  • Time Factors
  • Tissue Distribution

Substances

  • Growth Substances
  • Activins
  • Bleomycin
  • Inhibins