Posttransplant bronchiolitis obliterans syndrome is associated with bronchial epithelial to mesenchymal transition
MetadataShow full item record
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. © 2009 The American Society of Transplantation and the American Society of Transplant Surgeons.
Showing items related by title, author, creator and subject.
Regional Differences in Susceptibiity of Bronchial Epithelium to Mesenchymal Transition and Inhibition by the Macrolide Antibiotic AzithromycinBanerjee, B.; Musk, M.; Sutanto, E.; Yerkovich, S.; Hopkins, P.; Knight, D.; Lindsey-Temple, S.; Stick, S.; Kicic, Anthony; Chambers, D. (2012)Objective: Dysregulated repair following epithelial injury is a key forerunner of disease in many organs, and the acquisition of a mesenchymal phenotype by the injured epithelial cells (epithelial to mesenchymal transition, ...
Cells of Epithelial Lineage Are Present in Blood, Engraft the Bronchial Epithelium, and Are Increased in Human Lung TransplantationMay, L.A.; Kicic, Anthony ; Rigby, P.; Heel, K.; Pullen, T.L.; Crook, M.; Charles, A.; Banerjee, B.; Ravine, D.; Saxena, A.; Musk, M.; Stick, S.M.; Chambers, D.C. (2009)Background: There is a growing expectation that cell-based therapies will prove effective for a wide range of conditions including lung diseases such as cystic fibrosis. The promise of these therapies will depend largely ...
The airway epithelium is a direct source of matrix degrading enzymes in bronchiolitis obliterans syndromeBanerjee, B.; Ling, K.; Sutanto, E.; Musk, M.; Yerkovich, S.; Hopkins, P.; Stick, S.; Kicic, Anthony; Chambers, D. (2011)Background: Long-term survival after lung transplantation is hindered by the development of bronchiolitis obliterans syndrome (BOS), and recent evidence suggests that dysregulated epithelial repair may underlie its ...