Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease

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. Su...

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Bibliographic Details
Published in:Respiratory research Vol. 12; no. 1; p. 130
Main Authors: Sohal, Sukhwinder S, Reid, David, Soltani, Amir, Ward, Chris, Weston, Steven, Muller, H Konrad, Wood-Baker, Richard, Walters, E Haydn
Format: Journal Article
Language:English
Published: London BioMed Central 05.10.2011
BioMed Central Ltd
Nature Publishing Group
BMC
Subjects:
Aged
Analysis
Antigenic determinants
B cells
Care and treatment
Chronic obstructive pulmonary disease
clefts
cytokeratin
epithelial mesenchymal transition (EMT)
Epithelial-Mesenchymal Transition - physiology
Female
Genotype & phenotype
Health aspects
Histology
Human subjects
Humans
Inflammation - diagnosis
Inflammation - metabolism
Inflammation - pathology
inflammatory cells and S100A4
Keratin
Lung diseases, Obstructive
Lymphocytes
Male
Matrix Metalloproteinase 9 - biosynthesis
Medicine
Medicine & Public Health
Mesoderm - enzymology
Mesoderm - metabolism
Mesoderm - pathology
Middle Aged
Pneumology/Respiratory System
Pulmonary Disease, Chronic Obstructive - enzymology
Pulmonary Disease, Chronic Obstructive - metabolism
Pulmonary Disease, Chronic Obstructive - pathology
Respiratory Mucosa - enzymology
Respiratory Mucosa - metabolism
Respiratory Mucosa - pathology
Smokers
Smoking - adverse effects
Smoking - metabolism
Smoking - pathology
Statistical analysis
Stem cells
T cells
Australia
United Kingdom
epithelial mesenchymal transition (EMT)
clefts
inflammatory cells and S100A4
cytokeratin
ISSN:1465-993X, 1465-9921, 1465-993X
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Summary: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.
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ISSN:1465-993X
1465-9921
1465-993X
DOI:10.1186/1465-9921-12-130