Posttransplant bronchiolitis obliterans syndrome is associated with bronchial epithelial to mesenchymal transition

Hodge, S., Holmes, M., Banerjee, B., Musk, M., Kicic, A., Waterer, G., Reynolds, P. N., Hodge, G. and Chambers, D. C. (2009) Posttransplant bronchiolitis obliterans syndrome is associated with bronchial epithelial to mesenchymal transition. American Journal of Transplantation, 9 4: 727-733. doi:10.1111/j.1600-6143.2009.02558.x


Author Hodge, S.
Holmes, M.
Banerjee, B.
Musk, M.
Kicic, A.
Waterer, G.
Reynolds, P. N.
Hodge, G.
Chambers, D. C.
Title Posttransplant bronchiolitis obliterans syndrome is associated with bronchial epithelial to mesenchymal transition
Journal name American Journal of Transplantation   Check publisher's open access policy
ISSN 1600-6135
1600-6143
Publication date 2009-04-01
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1600-6143.2009.02558.x
Open Access Status DOI
Volume 9
Issue 4
Start page 727
End page 733
Total pages 7
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Bronchiolitis obliterans syndrome (BOS) compromises lung transplant outcomes and is characterised by airway epithelial damage and fibrosis. The process whereby the normal epithelial configuration is replaced by fibroblastic scar tissue is poorly understood, but recent studies have implicated epithelial mesenchymal transition (EMT). The primary aim of this study was to assess the utility of flow cytometry in detecting and quantifying EMT in bronchial epithelial cells.
Formatted abstract
Bronchiolitis obliterans syndrome (BOS) compromises lung transplant outcomes and is characterised by airway epithelial damage and fibrosis. The process whereby the normal epithelial configuration is replaced by fibroblastic scar tissue is poorly understood, but recent studies have implicated epithelial mesenchymal transition (EMT). The primary aim of this study was to assess the utility of flow cytometry in detecting and quantifying EMT in bronchial epithelial cells. Large airway brushings were obtained at 33 bronchoscopies in 16 BOS-free and 6 BOS grade 1-3 patients at 2-120 months posttransplant. Flow cytometry was used to assess expression of the mesenchymal markers αSMA, S100A4 and ED-A FN and HLA-DR. TGF β1 and HGF were measured in Bronchoalveolar lavage (BAL). Expression of all three mesenchymal markers was increased in BOS, as was HLA-DR. BAL HGF, but not TGF β1 was increased in BOS. Longitudinal investigation of one patient revealed a 100% increase in EMT markers concurrent with a 6-fold increase in BAL TGF β1 and the diagnosis of BOS at 17 months posttransplant. Flow cytometric evaluation of bronchial epithelium may provide a novel and rapid means to assess lung allografts at risk of BOS.
Keyword Bronchiolitis obliterans syndrome
Epithelial mesenchymal transition
Flow cytometry
Lung transplantation
Obilterative bronchiolitis
Hepatocyte Growth-Factor
Lung-Transplant Recipients
Bronchoalveolar Lavage
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 5018121
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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