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Experimental bleomycin lung in mice

A contribution to the pathogenesis of pulmonary fibrosis

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Abstract

In long term studies over a period of 120 days, staggered intraperitoneal doses (0.15 mg to 18 mg) of the cytostatic polypeptide bleomycin were given to NMRI mice to produce pulmonary fibroses. The onset and progression of the lung reaction was monitored at 5-day intervals by light and electron microscopy. On the basis of the morphological alterations, a pathogenetic chain of events is postulated for pulmonary fibrosis: The primary lesions arises in the alveolar capillaries, with endothelial swelling and interstitial oedema. Thickening of the alveolar wall leads to a reactive proliferation of type II pneumocytes with overproduction of surfactant. As a result of the disturbed monomolecular spreading of surfactant on the inner alveolar surface, giant lammellar bodies are formed in type II pneumocytes. These type II cells become necrotic, and free surfactant present in the alveoli is phagocytized by monocytic alveolar macrophages. The macrophages perish and release mediators which activate fibroblasts resulting in fibrillogenesis. It is postulated that by continuous production of surfactant and migration of monocytes from the blood stream the course of pulmonary fibrosis, once started, can be self-perpetuating, even after the etiological factor is no longer present.

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Authors and Affiliations

  1. Division of Pathology, Research Institute Borstel, Institute for Experimental Biology and Medicine, Parkallee, D-2061, Borstel

    E. Fasske & K. Morgenroth

  2. Institute of Pathology, Ruhr-University, D-4630, Bochum, Federal Republic of Germany

    E. Fasske & K. Morgenroth

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  1. E. Fasske
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  2. K. Morgenroth
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Dedicated to Professor G. Dhom (Homburg/Saar) on the occasion of his 60th birthday

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Fasske, E., Morgenroth, K. Experimental bleomycin lung in mice. Lung 161, 133–146 (1983). https://doi.org/10.1007/BF02713855

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  • DOI: https://doi.org/10.1007/BF02713855

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