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Resistance of TNF/LTα double deficient mice to bleomycin‐induced fibrosis
Author(s) -
PIGUET PIERRE F.,
KAUFMAN STEPHEN,
BARAZZONE CONSTANCE,
MULLER MATTHIAS,
RYFFEL BERNHARD,
EUGSTER HANS P.
Publication year - 1997
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1046/j.1365-2613.1997.d01-240.x
Subject(s) - bleomycin , tumor necrosis factor alpha , fibrosis , medicine , cancer research , chemistry , immunology , pathology , chemotherapy
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.