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Am J Physiol Lung Cell Mol Physiol 283: L867-L873, 2002. First published June 21, 2002; doi:10.1152/ajplung.00020.2002
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Vol. 283, Issue 4, L867-L873, October 2002

Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases

Richard E. K. Russell1, Andrew Thorley2, Sarah V. Culpitt1, Sara Dodd1, Louise E. Donnelly1, Carmen Demattos1, Mary Fitzgerald2, and Peter J. Barnes1

1 Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY; and 2 Bayer Pharmaceuticals, Stoke Poges SL2 4AE, United Kingdom

Chronic obstructive pulmonary disease (COPD) is a common lung disease with cigarette smoking as the major etiological factor, but only 15% of smokers develop COPD. Destruction of lung elastin observed in COPD is mediated by many enzymes, including cysteine, serine, and matrix metalloproteinases (MMP). The contribution of these enzymes to the lung elastolytic load, released from alveolar macrophages collected from nonsmokers, healthy smokers, and COPD patients, was examined by radiolabeled elastin as substrate in the presence of specific enzyme inhibitors. The activity of MMP was further examined by zymography and Western blotting. COPD macrophages degraded more elastin than either of the other groups. Elastolysis was greatest in the initial 24 h. Through the 72-h culture period, the contribution to elastolysis of serine elastases decreased, MMP increased, and cysteine elastases remained constant. The increased release of elastolytic enzymes in COPD subjects may explain why some smokers develop COPD. This difference may be due to unknown susceptibility factors. Serine proteases play a significant role; however, other enzymes, particularly the MMP, deserve further investigation.

chronic obstructive pulmonary disease


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