Posttransplant Bronchiolitis Obliterans Syndrome Is Associated with Bronchial Epithelial to Mesenchymal Transition

被引：63

作者：

Hodge, S. ^{[1
]}

Holmes, M. ^{[1
,2
]}

Banerjee, B. ^{[3
,4
]}

Musk, M. ^{[3
]}

Kicic, A. ^{[5
]}

Waterer, G. ^{[4
]}

Reynolds, P. N. ^{[1
]}

Hodge, G. ^{[1
]}

Chambers, D. C. ^{[4
,6
]}

机构：

[1] Hanson Inst, Lung Res Lab, Adelaide, SA, Australia

[2] Royal Adelaide Hosp, S Australian Lung Transplant Serv, Adelaide, SA 5000, Australia

[3] Royal Perth Hosp, Western Australian Lung Transplant Program, Perth, WA, Australia

[4] Univ Western Australia, Perth, WA 6009, Australia

[5] Telethon Inst Child Hlth Res, Perth, WA, Australia

[6] Prince Charles Hosp, Queensland Ctr Pulm Transplantat & Vasc Dis, Brisbane, Qld 4032, Australia

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2009年 / 9卷 / 04期

基金：

英国医学研究理事会;

关键词：

Bronchiolitis obliterans syndrome; epithelial mesenchymal transition; flow cytometry; lung transplantation; obilterative bronchiolitis; HEPATOCYTE GROWTH-FACTOR; LUNG-TRANSPLANT RECIPIENTS; BRONCHOALVEOLAR LAVAGE; TGF-BETA; PHENOTYPE; FIBROSIS; CELLS; DISEASE;

D O I：

10.1111/j.1600-6143.2009.02558.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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 alpha SMA, S100A4 and ED-A FN and HLA-DR. TGF beta 1 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 beta 1 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 beta 1 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.

引用

页码：727 / 733

页数：7

共 20 条

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