Bleomycin-induced pulmonary fibrosis in animals (IPF model)

Bleomycin-induced pulmonary fibrosis in animals

Idiopathic pulmonary fibrosis (IPF) is a severe chronic lung disease causing irreversible dysfunction of the organ. It is characterized by an abnormal repair process, causing uncontrolled deposition of extracellular matrix (ECM) including collagen, excessive proliferation of fibroblasts, and destruction of the cellular architecture of the lung. Bleomycin-induced pulmonary fibrosis in laboratory animals is a very well-characterized model, which can be used to study pathomechanisms directly related to human pulmonary fibrosis.

The challenge involves single or repeated exposure to bleomycin using a three or four-week protocol. This exposure has been shown to reproduce hallmarks of human fibrosis, including interstitial lung fibrosis, multifocal alveolar emphysema, accumulation of pigment-laden macrophages, and chronic active inflammation.

Endpoints/outcome parameters

  • Pulmonary fibrosis
  • Alveolar emphysema
  • Right heart hypertrophy

Readout parameters

  • In-life assessment of lung function: invasive, repetitive technique; dynamic compliance and lung resistance
  • Animal and gross pathology: animal survival, decrease in body weight, increase in lung weight, weight of right ventricle and Fulton index to quantify right heart hypertrophy
  • Bronchoalveolar lavage: total and differential cell counts by flow cytometry, cytokine levels by ELISA or MSD
  • Histology imaging: conventional stainings, histopathology, histomorphometrical analysis, immunohistochemistry, and pathology scoring of fibrosis
  • Lung tissue analysis: RNA isolation for gene expression analysis, cytokine levels by ELISA or MSD, hydroxyproline assay

Publications

  1. Srivastava M, Steinwede K, Kiviranta R, Morko J, Hoymann HG, Laenger F, Buehling F, Welte T, Maus U. Overexpression of cathepsin K in mice decreases collagen deposition and lung resistance in response to bleomycin-induced pulmonary fibrosis. Respiratory Research 9 (2008): 54.
  2. Ueberberg B, Janze AK, Steinwede K, Maus R, Mägel L, Hoymann HG, Braun A, Länger F, Jonigk D, Gauldie J, Welte T, Maus UA. Bacterial infection triggers exacerbation of established pulmonary fibrosis in mice: impact on lung protective immunity. Am J Respir Crit Care Med 185 (2012): A3921.
  3. Hoymann, HG, Ernst H, Creutzenberg O, Schaudien D, Müller M, Knudson L, Braun A. Invasive but repetitive lung function measurements in a rodent model of pulmonary fibrosis. Am J Respir Crit Care Med 189 (2014): A1952.
  4. Hoymann, HG, Schaudien D, Hansen T, Müller M, Braun A. Comparison of fibrotic and emphysematous alterations in the lungs of bleomycin-treated rats and hamsters. Am J Respir Crit Care Med 191 (2015): A3454.
  5. Hoymann HG, Schaudien D, Hansen T, Niehof M, Braun A. Functional, histological and biochemical endpoints for assessing antifibrotic efficacy in a rat model of pulmonary fibrosis . Am J Respir Crit Care Med 2016 (in press).