Sohal, SS and Reid, D and Soltani, A and Ward, C and Weston, S and Muller, HK and Wood-Baker, R and Walters, EH, Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease, Respiratory Research , 12 Article 130. ISSN 1465-993X (2011) [Refereed Article]
© 2011 Floreth et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Official URL: http://dx.doi.org/10.1186/1465-9921-12-130
Background: The reticular basement membrane (Rbm) in smokers and especially smokers
with COPD is fragmented with "clefts" containing cells staining for the collagenase
matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4. These cells are also
present in the basal epithelium. Such changes are likely hallmarks of epithelial
mesenchymal transition (EMT). We aimed to confirm the epithelial origin of these Rbm
cells, and to exclude potential confounding by infiltrating inflammatory cells.
Methods: Endobronchial biopsy sections from 17 COPD current smokers, with
documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil
marker), CD68 (macrophage / mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells),
CD11c (dendritic cells / inflammatory cells), and S100 (Langerhans cells). The
number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers
were then compared to numbers staining for S100A4, "a documented EMT epitope".
Slides were double stained for S100A4 and cytokeratin(s).
Results: In the basal epithelium significantly more cells stained for S100A4 compared to
infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 – 37.3) versus 0 (0
– 9.6) per mm, p<0.003. Markedly more S100A4 staining cells were also observed in the
Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any
sub-type: 58 (37.3 – 92.6) versus 0 (0 – 4.8) cells/mm Rbm, p<0.003. Cells in the basal
epithelium 26 (21.3 – 37.3) per mm) and Rbm (5.9 (2.3 – 13.8) per mm) frequently double
stained for both cytokeratin and S100A4.
Conclusions: These data provide additional support for active EMT in COPD airways.
|Item Type:||Refereed Article|
|Keywords:||cytokeratin, clefts, epithelial mesenchymal transition (EMT), inflammatory cells and S100A4|
|Research Division:||Medical and Health Sciences|
|Research Group:||Cardiovascular Medicine and Haematology|
|Research Field:||Respiratory Diseases|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Respiratory System and Diseases (incl. Asthma)|
|Creator:||Sohal, SS (Dr Sukhwinder Sohal)|
|Creator:||Reid, D (Dr David Reid)|
|Creator:||Soltani, A (Dr Amir Soltani Abhari)|
|Creator:||Weston, S (Mr Steven Weston)|
|Creator:||Muller, HK (Professor Konrad Muller)|
|Creator:||Wood-Baker, R (Professor Richard Wood-Baker)|
|Creator:||Walters, EH (Professor Haydn Walters)|
|Deposited By:||Menzies Research Institute Tasmania|
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