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Effect of irradiation/bone marrow transplantation on alveolar epithelial type II cells is aggravated in surfactant protein D deficient mice

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Abstract

Irradiation followed by bone marrow transplantation (BM-Tx) is a frequent therapeutic intervention causing pathology to the lung. Although alveolar epithelial type II (AE2) cells are essential for lung function and are damaged by irradiation, the long-term consequences of irradiation and BM-Tx are not well characterized. In addition, it is unknown whether surfactant protein D (SP-D) influences the response of AE2 cells to the injurious events. Therefore, wildtype (WT) and SP-D−/− mice were subjected to a myeloablative whole body irradiation dose of 8 Gy and subsequent BM-Tx and compared with age- and sex-matched untreated controls. AE2 cell changes were investigated quantitatively by design-based stereology. Compared with WT, untreated SP-D−/− mice showed a higher number of larger sized AE2 cells and a greater amount of surfactant-storing lamellar bodies. Irradiation and BM-Tx induced hyperplasia and hypertrophy in WT and SP-D−/− mice as well as the formation of giant lamellar bodies. The experimentally induced alterations were more severe in the SP-D−/− than in the WT mice, particularly with respect to the surfactant-storing lamellar bodies which were sometimes extremely enlarged in SP-D−/− mice. In conclusion, irradiation and BM-Tx have profound long-term effects on AE2 cells and their lamellar bodies. These data may explain some of the clinical pulmonary consequences of this procedure. The data should also be taken into account when BM-Tx is used as an experimental procedure to investigate the impact of bone marrow-derived cells for the phenotype of a specific genotype in the mouse.

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Acknowledgments

The authors wish to thank Olaf Bahlmann, Susanne Fassbender, Jan Hegermann, Susanne Kuhlmann and Christa Lichtenberg for technical help.

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    Authors and Affiliations

    1. Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany

      Christian Mühlfeld, Jan Philipp Schneider, Julia Schipke, Dennis Lutz, Bastian Birkelbach, Lars Knudsen & Matthias Ochs

    2. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany

      Christian Mühlfeld, Lars Knudsen & Matthias Ochs

    3. Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany

      Christian Mühlfeld & Matthias Ochs

    4. Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK

      Jens Madsen, Rose-Marie Mackay & Howard Clark

    5. Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK

      Jens Madsen

    6. National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK

      Jens Madsen

    7. Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK

      Marina Botto

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    Christian Mühlfeld and Jens Madsen have contributed equally and share first authorship.

    Matthias Ochs and Howard Clark have contributed equally and share senior authorship.

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    Mühlfeld, C., Madsen, J., Mackay, RM. et al. Effect of irradiation/bone marrow transplantation on alveolar epithelial type II cells is aggravated in surfactant protein D deficient mice. Histochem Cell Biol 147, 49–61 (2017). https://doi.org/10.1007/s00418-016-1479-7

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