A total fibrinogen deficiency is compatible with the development of bleomycininduced pulmonary fibrosis in mice

V. A. Ploplis, J. Wilberding, I. Cornelissen, E. Defokdm, Z. Uang, E. D. Rosen, F. J. Castellino

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Abstract

Previous in vivo studies have implicated fibrin as an important effector molecule for facilitating the fibroproliferative response following acute lung injury. In order to further investigate the effect of fibrin on the development of pulmonary fibrosis, this study utilized fibrinogen-deficient (Fg+ and wild-type (W7) mice in a bleomycin model of pulmonary fibrosis. Fg+ mice were developed by targeted deletion of the y chain of murine fibrinogen. Fibrinogen α, β, or γ chains were not detected in circulating plasma by Western blot analysis. The genotypic distribution of offspring from crosses of Fg+ parents followed the expected Mendelian pattern indicating the fibrinogen deficiency does not cause embryonic lethality. A number of Fg+ neonates presented with spontaneous bleeding in various anatomical locations, but for the most part were able to resolve these bleeding episodes and survive. For the pulmonary fibrosis study, a bleomycin solution was delivered non-invasively in WT and Fg'- mice. Two weeks after administration, anesthetized mice were perfused and the left lung was removed for quantitation of the extent of fibrosis by measuring collagen levels. The right lung was inflated with fixative and processed for histological analysis. Trichrome-stained sections confirmed the presence of collagen-rich fibrotic areas within the interstium in both Fg:- and WTmice treated with bleomycin. These studies suggest that the development of bleomycininduced pulmonary fibrosis is not dependent on the presence of fibrin(ogen).

Original languageEnglish (US)
Number of pages1
JournalFibrinolysis and Proteolysis
Volume14
Issue numberSUPPL. 1
StatePublished - Dec 1 2000

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ASJC Scopus subject areas

  • Hematology

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Ploplis, V. A., Wilberding, J., Cornelissen, I., Defokdm, E., Uang, Z., Rosen, E. D., & Castellino, F. J. (2000). A total fibrinogen deficiency is compatible with the development of bleomycininduced pulmonary fibrosis in mice. Fibrinolysis and Proteolysis, 14(SUPPL. 1).