Role of diminished epithelial GM-CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis

Paul J. Christensen, Marc B. Bailie, Richard E. Goodman, Aidan D. O'Brien, Galen B. Toews, Robert Paine

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Evidence derived from human and animal studies strongly supports the notion that dysfunctional alveolar epithelial cells (AECs) play a central role in determining the progression of inflammatory injury to pulmonary fibrosis. We formed the hypothesis that impaired production of the regulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) by injured AECs plays a role in the development of pulmonary fibrosis. To test this hypothesis, we used the well-characterized model of bleomycin-induced pulmonary fibrosis in rats. GM-CSF mRNA is expressed at a constant high level in the lungs of untreated or saline-challenged animals. In contrast, there is a consistent reduction in expression of GM-CSF mRNA in the lung during the first week after bleomycin injury. Bleomycin-treated rats given neutralizing rabbit anti-rat GM-CSF IgG develop increased fibrosis. Type II AECs isolated from rats after bleomycin injury demonstrate diminished expression of GM-CSF mRNA immediately after isolation and in response to stimulation in vitro with endotoxin compared with that in normal type II cells. These data demonstrate a defect in the ability of type II epithelial cells from bleomycin-treated rats to express GMCSF mRNA and a protective role for GM-CSF in the pathogenesis of bleomycin-induced pulmonary fibrosis.

Original languageEnglish (US)
Pages (from-to)L487-L495
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number3 23-3
StatePublished - Oct 4 2000

Keywords

  • Alveolar epithelial cells
  • Animal model
  • Granulocyte-macrophage colony-stimulating factor
  • Growth factors
  • Lung injury

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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