REQUIREMENT FOR MACROPHAGE ELASTASE FOR CIGARETTE SMOKE-INDUCED EMPHYSEMA IN MICE

To determine which proteinases are responsible for the lung destructio n characteristic of pulmonary emphysema, macrophage elastase-deficient (MME-/-) mice were subjected to cigarette smoke. In contrast to wild- type mice, MME-/- mice did not have increased numbers of macrophages i n their lungs and did not develop emphysema in response to long-term e xposure to cigarette smoke. Smoke-exposed MME-/- mice that received mo nthly intratracheal instillations of monocyte chemoattractant protein- 1 showed accumulation of alveolar macrophages but did not develop air space enlargement. Thus, macrophage elastase is probably sufficient fo r the development of emphysema that results from chronic inhalation of cigarette smoke.