Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema [State of the Art Series. Chronic obstructive pulmonary disease in high- and low-income countries. Edited by G. Marks and M. Chan-Yeung. Number 3 in the series]
In subjects who do not have antitrypsin deficiency, the case for elastolytic injury by neutrophils causing emphysema is less definite, because of the lack of a severe deficiency of active α1-ntitrypsin leading to unopposed elastolysis by neutrophil elastase. It is likely that alveolar macrophages play a pathogenic role in emphysema; they express potent elastolytic enzymes, cathepsins and matrix metalloproteases (MMPs), which are induced by smoking. The numbers of macrophages are increased in the region of the respiratory bronchiole, where centrilobular emphysema develops in smokers. Macrophage cathepsins are inhibited by an antiprotease cystatin C, while the MMPs are inhibited by the tissue inhibitors of metalloproteases (TIMPs).
Some pro-inflammatory mediators induce release of MMPs from macrophages without inducing increase in TIMPs, leading to possible protease-antiprotease imbalance. Studies of proteases in alveolar macrophages obtained by bronchoalveolar lavage and studies on lung tissue indicate increased protease expression in subjects with chronic obstructive pulmonary disease (COPD) compared to subjects without COPD.
Document Type: Invited Paper
Affiliations: 1: Division of Respiratory Medicine, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada 2: University of British Columbia Respiratory Division, Vancouver, British Columbia, Canada
Publication date: April 1, 2008
The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.
Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website
- Editorial Board
- Information for Authors
- Subscribe to this Title
- International Journal of Tuberculosis and Lung Disease
- Public Health Action
- Ingenta Connect is not responsible for the content or availability of external websites