Matrix Metalloproteinase-12 and Cathepsin D Expression in Pulmonary Macrophages and Dendritic Cells of Cigarette Smoke-Exposed Mice

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Abstract
An imbalance between proteinases and their inhibitors is believed to play an essential role in the development of chronic obstructive pulmonary disease (COPD) and pulmonary emphysema. COPD is mainly caused by cigarette smoking, and is characterized by an increase in inflammatory cells in small airways and lung parenchyma. We examined the mRNA expression of several proteinases in lungs of mice exposed to cigarette smoke or control air. After 1, 3 and 6 months’ smoke exposure there was a significant increase of matrix metalloproteinase (MMP)-12 and Cathepsin D mRNA, compared to air-exposed mice. To determine the cellular origin of MMP-12 and Cathepsin D, we isolated dendritic cells (DCs) and macrophages from the lungs of mice. There was an increase in MMP-12 mRNA after smoke exposure in both macrophage and DC populations, whereas Cathepsin D was predominantly expressed in macrophages. Immunohistochemistry clearly revealed the expression of Cathepsin D protein in alveolar macrophages of cigarette smoke-exposed mice, in contrast to air-exposed littermates. Western blots on lung tissue demonstrated an increase of MMP-12 protein in cigarette smoke-exposed animals. These results indicate that cigarette smoke increases the expression of MMP-12 and Cathepsin D in the lungs of mice, and that not only macrophages but also DCs produce MMP-12.

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