Resistance of TNF/LTα double deficient mice to bleomycin‐induced fibrosis

PF PIGUET, S KAUFMAN… - International journal …, 1997 - Wiley Online Library
PF PIGUET, S KAUFMAN, C BARAZZONE, M MULLER, B RYFFEL, HP EUGSTER
International journal of experimental pathology, 1997Wiley Online Library
In order to evaluate the role and mode of action of TNF in bleomycin‐induced lung fibrosis,
mice deficient for TNF and LTα (ΔTNF/LTα) were examined at 2 months of age and after 3
weekly iv injections of bleomycin. The body weight of the ΔTNF/LTα 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 ΔTNF/LTα, mice …
In order to evaluate the role and mode of action of TNF in bleomycin‐induced lung fibrosis, mice deficient for TNF and LTα (ΔTNF/LTα) were examined at 2 months of age and after 3 weekly i.v. injections of bleomycin. The body weight of the ΔTNF/LTα 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 ΔTNF/LTα, mice. Lymphoid infiltration was also prominent in wild type, but absent from ΔTNF/LTα, mice. Bleomycin injections increased collagen deposition, as evaluated by the lung hydroxyproline content, more markedly in wild type, than in ΔTNF/LTα, 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 ΔTNF/LTα, mice. This study indicates that the expression of TNF/LTα 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.
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