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Comparison of two models of bleomycin-induced lung fibrosis in mouse on the level of leucocytes and T cell subpopulations in bronchoalveolar lavage

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Abstract

Bleomycin produces pulmonary fibrosis in mice when given as a single intratracheal instillation or as multiple subcutaneous injections. Both models are associated with a significant deposition of collagen in the lungs but differ in the location of the initial lesions. Intratracheal instillation of bleomycin directs lesions to peribronchial or peribronchiolar sites, whereas subcutaneous injection produces lesions in subpleural and perivascular locations. It was therefore of interest to analyse the bronchoalveolar lavage (BAL) fluid for differences in the cellular composition, especially of intraepithelial T lymphocytes characterised by the expression of the integrin αEβ7.

Intracheal instillation of bleomycin induced a 5 to 6 times higher number of neutrophils and lymphocytes in BAL fluid than the subcutaneous model. Furthermore, intratracheal instillation of bleomycin induced the infiltration of eosinophilic neutrophils, a peculiar subtype of neutrophils often found in rodents, which were not found in BAL after subcutaneous injection of bleomycin. In both models of bleomycin injection, however, CD4+, CD8+, NK, and γδ T lymphocytes were detected with dominance of the CD4+ T cell population. Analysis of the expression of the integrin αEβ7 revealed similar numbers of αEβ7+ cells in the CD4+ and γδ T cell populations in both models but significantly lower numbers of αEβ7+ T cells were found in the BAL fluid within the CD8+ T cell population after subcutaneous injection of bleomycin compared to intratracheal instillation.

These results show that a difference in route of bleomycin administration not only causes changes in the localisation of the lesions but that this variation may be reflected in alterations within the BAL leucocyte population especially within the intraepithelial T lymphocytes.

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Authors and Affiliations

  1. Department of Molecular Biosciences, University of California, Davis, CA, USA

    R. K. Braun & Shiri N. Giri (Professor and Chairman)

  2. Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA, USA

    D. A. Ferrick

  3. Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA

    A. Sterner-Kock & D. M. Hyde

  4. Department of Cell Biology, The Babraham Institute, Cambridge, UK

    P. J. Kilshaw

Authors
  1. R. K. Braun
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  2. D. A. Ferrick
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  3. A. Sterner-Kock
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  4. P. J. Kilshaw
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  5. D. M. Hyde
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  6. Shiri N. Giri
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Braun, R.K., Ferrick, D.A., Sterner-Kock, A. et al. Comparison of two models of bleomycin-induced lung fibrosis in mouse on the level of leucocytes and T cell subpopulations in bronchoalveolar lavage. Comp Haematol Int 6, 141–148 (1996). https://doi.org/10.1007/BF00368457

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