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Obliterative airway remodelling in transplanted and non-transplanted lungs

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Abstract

Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far. Obliterated and unremodelled airways from explanted lungs (n = 19) from patients suffering from chronic allograft dysfunction, infection, graft-versus-host disease and toxic exposure were isolated by laser-assisted microdissection. Airways from lung allografts harvested shortly before and after transplantation (n = 4) as well as fibroblastic foci from lungs with interstitial pulmonary fibrosis (n = 4) served as references. Pre-amplified cDNA was analysed by quantitative real-time RT-PCR for expression of fibrosis, inflammation and apoptosis-associated genes. Composition of infiltrating cells and protein expression were assessed by conventional histology and immunohistochemistry. Bronchiolitis obliterans in transplanted patients showed a significant increase of BMP-7 expression (p = 0.0141 compared with controls), while TGF-β1 and FGF-2 as well as BMP-4 and BMP-7 were up-regulated in fibroblastic foci in interstitial pulmonary fibrosis (p < 0.0424 compared with controls). Regarding other fibrosis-associated genes (BMP-6, SMAD-3, CASP-3 and CASP-9, FASLG, NF-KB1, IL-1 and IL-2) as well as cellularity and cellular composition, no significant differences between obliterative airway remodelling in transplanted and non-transplanted patients could be shown. Obliterative airway remodelling in lung allografts and in non-transplanted patients share many morphological and genetic traits. BMPs, especially BMP-7, warrant further investigation as possible markers for the aggravation of airway remodelling.

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Acknowledgements

The authors would like to thank Gillian Teicke and Dr. Ho-Yen for editing the text.

Disclosure/conflicts of interest

This work is supported by a grant from the Deutsche Forschungsgemeinschaft (DFG, KFO 123 LTx, to Danny Jonigk and Hans Kreipe) and by the Integriertes Forschungs- und Behandlungszentrum Transplantation (BMBF, IFB-Tx). The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Danny Jonigk, Katharina Theophile, Kais Hussein, Oliver Bock, Ulrich Lehmann, Clemens L. Bockmeyer, Lavinia Maegel, Hans Kreipe & Florian Laenger

  2. Department of Pneumology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Jens Gottlieb & Tobias Welte

  3. Department of Cardiothoracic and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Stefan Fischer & Andre Simon

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  1. Danny Jonigk
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Correspondence to Danny Jonigk.

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Jonigk, D., Theophile, K., Hussein, K. et al. Obliterative airway remodelling in transplanted and non-transplanted lungs. Virchows Arch 457, 369–380 (2010). https://doi.org/10.1007/s00428-010-0949-x

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  • DOI: https://doi.org/10.1007/s00428-010-0949-x

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