title: Effect of irradiation/bone marrow transplantation on alveolar epithelial type II cells is aggravated in surfactant protein D deficient mice.
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.
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.|Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany.
authors: Christian
authors: C
authors: Mühlfeld
authors: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.|Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.|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.
authors: Jens
authors: J
authors: Madsen
authors: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK.
authors: Rose-Marie
authors: RM
authors: Mackay
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors: Jan Philipp
authors: JP
authors: Schneider
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors: Julia
authors: J
authors: Schipke
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors: Dennis
authors: D
authors: Lutz
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors: Bastian
authors: B
authors: Birkelbach
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
authors: Lars
authors: L
authors: Knudsen
authors: Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
authors: Marina
authors: M
authors: Botto
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.|Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany.
authors: Matthias
authors: M
authors: Ochs
authors: Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. h.w.clark@soton.ac.uk.
authors: Howard
authors: H
authors: Clark
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016026:Bone Marrow Transplantation; D005720:Gamma Rays; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000378:metabolism*; D014916:Whole-Body Irradiation
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D
keywords: Alveolar epithelium; Bone marrow transplantation; Design-based stereology; Irradiation; Surfactant