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Increased Activity of Matrix Metalloproteinase-8 and Matrix Metalloproteinase-9 in Induced Sputum From Patients With COPD^*

^* From the Departments of Respiratory Medicine (Drs. Vernooy and Wouters) and Medical Microbiology (Dr. Jacobs), Nutrition and Toxicology Research Institute Maastricht, University Hospital Maastricht, Maastricht, the Netherlands; the Department of Vascular Surgery (Dr. Lindeman), Leiden University Medical Center, Leiden, the Netherlands; and the Department of Biomedical Research (Dr. Hanemaaijer), TNO Prevention and Health, Leiden, the Netherlands.

Correspondence to: Juanita H. J. Vernooy, PhD, Department of Respiratory Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands; e-mail: j.vernooy{at}pul.unimaas.nl

Background: The increased expression of matrix metalloproteinases (MMPs) is considered to be a key factor in the development of COPD. Net MMP activity represents a tightly regulated process, which is not addressed by conventional investigation methods such as messenger RNA or protein expression. Yet, quantitative data on MMP activity in the airways of COPD patients are lacking.

Methods: We used specific immunocapture assays to quantify the activity of MMP collagenase (ie, MMP-1, MMP-8, and MMP-13) and MMP gelatinase (ie, MMP-2 and MMP-9) in the induced sputum of COPD patients (17 patients; FEV₁, 56% predicted) and healthy smokers (17 subjects; FEV₁, 99% predicted).

Results: Levels of total and active MMP-8 and MMP-9 were significantly increased in COPD patients vs control subjects, whereas MMP-1 activity levels were similar in both groups. The activity of MMP-2 and MMP-13 remained below the detection threshold of the assays. MMP-8 and MMP-9 activity were strongly related to neutrophilia in both groups, and the results of immunohistochemistry tests on sputum cytospins showed that MMP-9 was expressed in both alveolar macrophages and neutrophils, whereas MMP-8 expression was exclusively observed in neutrophils. A positive correlation was found between sputum MMP-8 and MMP-9 activity and the degree of airflow limitation.

Conclusion: We demonstrate increased MMP-8 and MMP-9 activity in the airway compartment of patients with mild-to-moderate COPD. This study provides further evidence of an impaired proteinase-antiproteinase balance in COPD patients.

Key Words: airway inflammation • collagenase • COPD • gelatinase • immunocapture activity assay

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