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Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat

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Abstract

Pulmonary fibrosis is characterized by excessive extracellular matrix deposition with concomitant loss of gas exchange units, and endothelin-1 (ET-1) has been implicated in its pathogenesis. Increased levels of ET-1 from tissues and bronchoalveolar lavage have been reported in patients with pulmonary fibrosis and in animal models after intratracheal bleomycin. We characterized the cellular distribution of alveolar ET receptors by immunohistochemistry in bleomycin-induced pulmonary fibrosis in the rat and determined the regulation by bleomycin of ET receptor mRNA expression in isolated alveolar macrophages and rat lung fibroblasts. We found significant increases in the numbers of fibroblasts and macrophages at day 7 compared to day 28 and control animals. ETB receptor immunoreactivity was observed on fibroblasts and invading monocytes. Isolated fibroblasts expressed both ETA and ETB receptor mRNA, and ETA receptor mRNA was upregulated by bleomycin. Isolated resident alveolar macrophages expressed neither ETA nor ETB receptor mRNA which were also not induced by bleomycin. We conclude that, while ETB receptor stimulation of fibroblasts and monocytes recruited during bleomycin-induced lung injury exerts antagonistic effects on fibroblast collagen synthesis, the observed increase in the number of fibroblasts in vivo and upregulation of fibroblast ETA receptor mRNA by bleomycin in vitro point to a predominance of the profibrotic effects of ET receptor engagement.

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Acknowledgements

The authors thank Mrs. Silvia Bramke, Mrs. Petra Peche, and Mrs. Carola Nipproschke for excellent technical assistance. This work was funded by a grant from the Deutsche Forschungsgemeinschaft (DFG KO 1814/2-2)

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Authors and Affiliations

  1. Department of Anesthesiology, University Hospital Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

    Martina Wendel, Anna Petzold, Lilla Knels, Jörg-Uwe Bleyl & Thea Koch

  2. Department of Physiological Chemistry, Medical Faculty of the Technical University of Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

    Roland Koslowski

  3. Department of Anatomy, Medical Faculty of the Technical University of Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

    Michael Kasper

  4. Department of Cardiology, Medical Clinics II, Medical Faculty of the Technical University of Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

    Antje Augstein

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  1. Martina Wendel
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Correspondence to Martina Wendel.

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Wendel, M., Petzold, A., Koslowski, R. et al. Localization of endothelin receptors in bleomycin-induced pulmonary fibrosis in the rat. Histochem Cell Biol 122, 507–517 (2000). https://doi.org/10.1007/s00418-004-0708-7

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