Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

被引：83

作者：

Chaudhuri, Rekha

McSharry, Charles

Brady, Jeffrey ^{[2
,3
,4
]}

Donnelly, Iona

Grierson, Christal ^{[2
,3
,4
]}

McGuinness, Stephen ^{[2
,3
,4
]}

Jolly, Lisa

Weir, Christopher J. ^{[5
]}

Messow, C. Martina ^{[1
]}

Spears, Mark

Miele, Gino ^{[2
,3
,4
]}

Nocka, Karl ^{[2
,3
,4
]}

Crowther, Dan ^{[2
,3
,4
]}

Thompson, Joyce

Brannigan, Maureen

Lafferty, Jane

Sproule, Michael ^{[6
]}

MacNee, William ^{[7
]}

Connell, Martin ^{[7
]}

Murchison, John T. ^{[7
]}

Shepherd, Malcolm C.

Feuerstein, Giora ^{[2
,3
,4
]}

Miller, Douglas K. ^{[2
,3
,4
]}

Thomson, Neil C.

机构：

[1] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 OYN, Lanark, Scotland

[2] Pfizer Res, Translat Med Res Collaborat, Dundee, Scotland

[3] Pfizer Res, Translat Med Res Collaborat, Cambridge, MA USA

[4] Pfizer Res, Translat Med Res Collaborat, Collegeville, PA USA

[5] Univ Edinburgh, MRC Hub Trials Methodol Res, Edinburgh EH8 9YL, Midlothian, Scotland

[6] Gartnavel Royal Hosp, Dept Radiol, Glasgow G12 OYN, Lanark, Scotland

[7] Univ Edinburgh, Ctr Inflammat Res Med Phys & Clin Radiol, Edinburgh EH8 9YL, Midlothian, Scotland

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2012年 / 129卷 / 03期

关键词：

Matrix metalloproteinase 12; tissue inhibitor of metalloproteinases 1 and 2; MMP12; expression; emphysema; chronic obstructive pulmonary disease; asthma; smoker; INVESTIGATE AIRWAY INFLAMMATION; MACROPHAGE ELASTASE; CIGARETTE-SMOKING; SMOOTH-MUSCLE; MMP-12; EMPHYSEMA; SMOKERS; INCREASE; MARKERS; CELLS;

D O I：

10.1016/j.jaci.2011.12.996

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known. Objectives: We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD. Methods: In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (DLCO), and CT assessment of emphysema (percentage of low-attenuation areas at less 2950 Hounsfield units). Results: Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or DLCO values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity. Conclusions: Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema. (J Allergy Clin Immunol 2012; 129: 655-63.)

引用

页码：655 / U106

页数：17

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