Source: Annual Congress 2001 - Inflammation and genetics in airway disease
Disease area: Airway diseases

Abstract

COPD is characterized by the loss of pulmonary connective tissue mediated by matrix metalloproteinases (MMPs) leading to irreversible airway obstruction. In this context, elastin degradation is critical allowing to emphysema and consequently to a loss of elastic recoil of the lungs. Increased levels of MMPs are found in the bronchoalveolar lavage (BAL) fluid of patients with COPD. Studies in a mouse model have shown that exposure to cigarette smoke causes emphysema through a macrophage-dependent process and particularly MMP-12. In contrast to their wild-type littermates, MMP-12 knock-out mice do not develop emphysema when exposed to cigarette smoke. Although numerous studies hypothesized that similar macrophage-mediated mechanisms exist in human, very little work has been done so far to examine MMP-12 expression in human lung tissue of COPD patients. Thus we analysed the presence of MMP-12 in BAL and bronchial biopsies (BB) from COPD (n=6, including chronic bronchitis with airflow limitation and emphysema) and control (n=6) subjects. Using immunocytochemistry, we demonstrated that MMP-12 was highly expressed in BAL cells and BB of COPD patients compared to smoker and non-smoker control subjects (P<0.05). MMP-12 was expressed in macrophage-rich areas as demonstrated by CD68 immunostaining on serial BB sections. This study reports for the first time MMP-12 protein expression in lungs of COPD subjects. Our results suggest that MMP-12 might have an important role in airway remodeling associated with COPD and especially with emphysema.

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S. Molet, N. Amiot, C. Belleguic, H. Lena, J. M. Planquois, C. Bertrand, P. Delaval, V. Lagente (Rennes, Fresnes, France). Human macrophage elastase (MMP-12) expression in human emphysematous lungs: role in extracellular matrix remodelling in chronic obstructive pulmonary diseases (COPD). Eur Respir J 2001; 16: Suppl. 31, 3383

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