Resistance of TNF/LT alpha double deficient mice to bleomycin-induced fibrosis

Int J Exp Pathol. 1997 Feb;78(1):43-8. doi: 10.1046/j.1365-2613.1997.d01-240.x.


In order to evaluate the role and mode of action of TNF in bleomycin-induced lung fibrosis, mice deficient for TNF and LT alpha (delta TNF/LT alpha) were examined at 2 months of age and after 3 weekly i.v. injections of bleomycin. The body weight of the delta TNF/LT alpha mice was 88 +/- 11% of that of the wild type littermates. Lung collagen, evaluated by its hydroxyproline content, was also lower (81 +/- 9%) in mutant than in wild type littermates. Bleomycin induced a diffuse alveolitis with focal areas of alveolar remodelling in wild type but not in delta TNF/LT alpha, mice. Lymphoid infiltration was also prominent in wild type, but absent from delta TNF/LT alpha, mice. Bleomycin injections increased collagen deposition, as evaluated by the lung hydroxyproline content, more markedly in wild type, than in delta TNF/LT alpha, mice. Cell trapping in the alveolar capillaries was evaluated by semi-quantitative electron microscopy. Bleomycin markedly increased platelet trapping in the alveolar capillaries of wild type, but not of delta TNF/LT alpha, mice. This study indicates that the expression of TNF/LT alpha genes increases the deposition of collagen in both untreated and inflamed lung and that these genes may act, at least in part, by promoting platelet trapping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin
  • Blood Platelets / ultrastructure
  • Capillaries / ultrastructure
  • Collagen / metabolism
  • Female
  • Lung / metabolism
  • Lymphotoxin-alpha / metabolism*
  • Lymphotoxin-alpha / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Pulmonary Alveoli / blood supply
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Tumor Necrosis Factor-alpha / deficiency*
  • Tumor Necrosis Factor-alpha / physiology


  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • Bleomycin
  • Collagen