Elastin expression in very severe human COPD.
Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD. Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2-3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs. Compared with donors, non-COPD and stage 2-3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p<0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased. The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.
Deslee
G
G
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.|Service de Pneumologie CHU Reims, IFR53, Reims, France.
Woods
J C
JC
Dept of Radiology, Washington University School of Medicine, St Louis, MO, USA.|Dept of Physics, Washington University School of Medicine, St Louis, MO, USA.
Moore
C M
CM
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Liu
L
L
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Conradi
S H
SH
Dept of Radiology, Washington University School of Medicine, St Louis, MO, USA.
Milne
M
M
Dept of Physics, Washington University School of Medicine, St Louis, MO, USA.
Gierada
D S
DS
Dept of Radiology, Washington University School of Medicine, St Louis, MO, USA.
Pierce
J
J
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Patterson
A
A
Thoracic Surgery, Washington University School of Medicine, St Louis, MO, USA.
Lewit
R A
RA
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Battaile
J T
JT
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Holtzman
M J
MJ
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Hogg
J C
JC
James Hogg iCapture Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, BC, Canada.
Pierce
R A
RA
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
D000328:Adult; D000368:Aged; D004549:Elastin / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking
D012333:RNA, Messenger; D004549:Elastin