Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis

J Clin Invest. 1999 Jul;104(1):13-9. doi: 10.1172/JCI5628.


The Fas ligand is predominantly expressed in activated T lymphocytes and is one of the major effector molecules of cytotoxic T lymphocytes and natural killer cells. Previously, we found excessive apoptosis of epithelial cells and infiltrating lymphocytes expressing Fas ligand mRNA in the lung tissue of bleomycin-induced pulmonary fibrosis in mice. Here we demonstrated that the administration of a soluble form of Fas antigen or anti-Fas ligand antibody prevented the development of this model and that lpr and gld mice were resistant against the induction of pneumopathy. These results suggest that the Fas-Fas ligand pathway plays an essential role in the development of pulmonary fibrosis and that preventing this pathway could have therapeutic value in lung injury and fibrosis.

MeSH terms

  • Animals
  • Apoptosis*
  • Bleomycin / toxicity
  • Fas Ligand Protein
  • Humans
  • Hydroxyproline / analysis
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology
  • In Situ Nick-End Labeling
  • Killer Cells, Natural / immunology
  • Lung / chemistry
  • Lung / pathology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred ICR
  • Mice, Inbred MRL lpr
  • Mice, Mutant Strains
  • Phagocytosis
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control*
  • Recombinant Fusion Proteins / physiology
  • T-Lymphocytes, Cytotoxic / immunology
  • fas Receptor / genetics
  • fas Receptor / physiology*


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Immunoglobulin Fc Fragments
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • fas Receptor
  • Bleomycin
  • Hydroxyproline