Elevated MMP-12 protein levels in induced sputum from patients with COPD.
BACKGROUND
Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers.


METHODS
Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate.


RESULTS
Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1-42.1) v 6.7 (3.9-10.4) v 4.2 (2.4-11.3) v 6.1 (4.5-7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4-8.0) v 0.14 (0.1-0.2) microg/microl, p = 0.0002).


CONCLUSIONS
MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.
Demedts
I K
IK
Department of Respiratory Diseases, Ghent University Hospital 7K12-IE, De Pintelaan 185, B-9000 Ghent, Belgium. M.DemedtsIngelK@UGent.be
Morel-Montero
A
A
Lebecque
S
S
Pacheco
Y
Y
Cataldo
D
D
Joos
G F
GF
Pauwels
R A
RA
Brusselle
G G
GG
D000368:Aged; D000818:Animals; D000906:Antibodies / Q000032:analysis; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004229:Dithiothreitol; D004797:Enzyme-Linked Immunosorbent Assay; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D013183:Sputum / Q000378:metabolism*; D014797:Vital Capacity / Q000502:physiology
D000906:Antibodies; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; D004229:Dithiothreitol