Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease.
OBJECTIVE
In COPD, the airways are chronically inflamed, and we have now observed fragmentation of the reticular basement membrane (Rbm). This appears to be a hallmark of the process known as epithelial mesenchymal transition (EMT), in which epithelial cells migrate through the Rbm and differentiate into fibroblasts. The aim of this study was to confirm the extent and relevance of Rbm fragmentation in smokers and patients with COPD, and to undertake a preliminary analysis of some classical markers of EMT.


METHODS
Endobronchial biopsies from current smokers (CS; n = 17) and ex-smokers with COPD (ES; n = 15), smokers with normal lung function (NS; n = 16) and never-smoking control subjects (NC; n = 15) were stained for the EMT markers, S100A4, vimentin, epidermal growth factor receptor and matrix metalloproteinase-9.


RESULTS
Compared with NC, there was significant Rbm fragmentation in the CS, ES and NS groups, which was positively associated with smoking history in subjects with COPD. Staining for basal epithelial S100A4, epithelial epidermal growth factor receptor and matrix metalloproteinase-9 in cells within Rbm clefts, and for S100A4 in Rbm cells, was increased in the CS, NS and ES groups compared with the NC group. There was also increased Rbm cell S100A4 staining in the CS group compared with the ES and NS groups. Basal epithelial cell staining for S100A4 was inversely correlated with airflow limitation. Double staining for both S100A4 and vimentin further strengthened the likelihood that these changes represented active EMT.


CONCLUSIONS
This is the first detailed description of fragmentation and cellularity of the Rbm in smokers, which were most marked in subjects with COPD. The data are consistent with active EMT in these subjects.
Sohal
Sukhwinder S
SS
Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
Reid
David
D
Soltani
Amir
A
Ward
Chris
C
Weston
Steven
S
Muller
H Konrad
HK
Wood-Baker
Richard
R
Walters
Eugene H
EH
D000368:Aged; D001485:Basement Membrane / Q000473:pathology*; D001980:Bronchi / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008648:Mesoderm / Q000473:pathology*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D020545:Respiratory Mucosa / Q000473:pathology*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000032:analysis; D012907:Smoking / Q000009:adverse effects / Q000473:pathology*; D014746:Vimentin / Q000032:analysis
D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014746:Vimentin; C077591:S100A4 protein, human; D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9