Abstract
BACKGROUND: Matrix degradation in emphysema has long been attributed to the action of neutrophil elastase (NE). More recently a role for other proteases, particularly the matrix metalloproteinases (MMPs), in the pathogenesis of this disease has been proposed. To date, however, the presence of MMPs in the lungs of patients with emphysema has not been demonstrated. METHODS: Samples of bronchoalveolar lavage (BAL) fluid from 10 patients with emphysema and from control subjects matched for sex and current smoking status were assessed for collagenase, gelatinase, and NE activity. Pulmonary function tests and computed tomographic (CT) scans were carried out on all study subjects. RESULTS: Collagenase activity was detected in BAL fluid samples from all emphysematous patients but in only one smoking control (p < 0.001). Gelatinase B was present in six patients and in two smoking controls (p < 0.03). The concomitant presence of gelatinase B in complex with lipocalin (NGAL) in the gelatinase positive samples suggests that the neutrophil is a significant source of the gelatinase B observed. NE was detected in six of the 10 patients with emphysema and in two smoking controls (p < 0.01), indicating that collagenase was more useful in discriminating between disease and control groups than either NE or gelatinase B. No relationship was observed between any of the enzymes measured and pulmonary function or CT density score. CONCLUSIONS: This study demonstrates, for the first time, the presence of increased levels of matrix metalloproteinases in the lungs of patients with emphysema and suggests that, in BAL fluid, collagenase activity may be a better indicator of the presence of emphysema than elastase.
Full Text
The Full Text of this article is available as a PDF (115.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- D'Armiento J., Dalal S. S., Okada Y., Berg R. A., Chada K. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell. 1992 Dec 11;71(6):955–961. doi: 10.1016/0092-8674(92)90391-o. [DOI] [PubMed] [Google Scholar]
- Hibbs M. S., Hasty K. A., Seyer J. M., Kang A. H., Mainardi C. L. Biochemical and immunological characterization of the secreted forms of human neutrophil gelatinase. J Biol Chem. 1985 Feb 25;260(4):2493–2500. [PubMed] [Google Scholar]
- Horwitz A. L., Hance A. J., Crystal R. G. Granulocyte collagenase: selective digestion of type I relative to type III collagen. Proc Natl Acad Sci U S A. 1977 Mar;74(3):897–901. doi: 10.1073/pnas.74.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janoff A., Raju L., Dearing R. Levels of elastase activity in bronchoalveolar lavage fluids of healthy smokers and nonsmokers. Am Rev Respir Dis. 1983 May;127(5):540–544. doi: 10.1164/arrd.1983.127.5.540. [DOI] [PubMed] [Google Scholar]
- O'Connor C., Odlum C., Van Breda A., Power C., Fitzgerald M. X. Collagenase and fibronectin in bronchoalveolar lavage fluid in patients with sarcoidosis. Thorax. 1988 May;43(5):393–400. doi: 10.1136/thx.43.5.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Openshaw P. J., O'Donnell D. R. Asthma and the common cold: can viruses imitate worms? Thorax. 1994 Feb;49(2):101–103. doi: 10.1136/thx.49.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rennard S. I., Basset G., Lecossier D., O'Donnell K. M., Pinkston P., Martin P. G., Crystal R. G. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 1986 Feb;60(2):532–538. doi: 10.1152/jappl.1986.60.2.532. [DOI] [PubMed] [Google Scholar]
- Sherman C. B. Health effects of cigarette smoking. Clin Chest Med. 1991 Dec;12(4):643–658. [PubMed] [Google Scholar]
- Snider G. L. Emphysema: the first two centuries--and beyond. A historical overview, with suggestions for future research: Part 2. Am Rev Respir Dis. 1992 Dec;146(6):1615–1622. doi: 10.1164/ajrccm/146.6.1615. [DOI] [PubMed] [Google Scholar]
- Tetley T. D. New perspectives on basic mechanisms in lung disease. 6. Proteinase imbalance: its role in lung disease. Thorax. 1993 May;48(5):560–565. doi: 10.1136/thx.48.5.560. [DOI] [PMC free article] [PubMed] [Google Scholar]