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Am. J. Respir. Crit. Care Med., Volume 163, Number 3, March 2001, 786-791

Human Collagenase (Matrix Metalloproteinase-1) Expression in the Lungs of Patients with Emphysema

KAZUSHI IMAI, SEEMA S. DALAL, EDWARD S. CHEN, ROBERT DOWNEY, LARRY L. SCHULMAN, MARK GINSBURG, and JEANINE D'ARMIENTO

Division of Molecular Medicine and Division of Pulmonary Medicine, Department of Medicine; and Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York

Pulmonary emphysema is believed to result from an imbalance between proteolytic enzymes and their inhibitors. Multiple studies have examined the presence of various proteases within the bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease (COPD). However, to date extensive examination of the lung parenchyma for the expression of destructive enzymes has not yet been determined. The following study examines the lung parenchyma of 23 patients with emphysema and 8 normal control samples for the expression of matrix matalloproteinase-1 (MMP-1), MMP-12, and MMP-9. We report here that interstitial collagenase (MMP-1) RNA, protein, and activity are present in the lung parenchyma of patients with emphysema and not in the lung of normal control subjects. In contrast, metalloelastase (MMP-12) expression is absent in these samples. Immunohistochemistry studies localized MMP-1 to the Type II pneumocyte in patients with emphysema and not normal control subjects or smokers without emphysema. This observation demonstrates that the lung is altered in emphysema such that the Type II pneumocyte secretes MMP-1 and suggests that MMP-1 may be an important enzyme involved in the destruction of the lung in the human disease. In addition, the induction of a proteolytic enzyme within the Type II pneumocyte suggests that the cells within the lung itself are capable of producing degradative enzymes in this disease process.




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