Immunoelectron-microscopic demonstration of elastase in emphysematous lungs of tight-skin mice

The tight-skin (Tsk) mouse has recently been proposed as a genetic model of emphysema. A morphometric study has shown that emphysema develops quickly, between 15 days and 1 month after birth. Previous biochemical and ultrastructural investigations of the lungs of 1- and 2-month-old Tsk mice revealed the presence of an ongoing elastolytic process. The goal of the present study was to investigate the role of mouse leukocyte elastase (MLE) in the development of emphysema in 1-month-old Tsk mice. Using electron microscopy and an immunogold labeling technique with rabbit anti-MLE IgG, MLE was localized within the lung neutrophils of control and Tsk mice. MLE was also found associated with elastin in the alveolar septa of Tsk but not of control mice. Little or no labeling was associated with other components (collagen, pneumocytes, and endothelium) of alveolar septa of Tsk mice. Lung elastin of control mice, or of control mice rendered emphysematous with porcine pancreatic elastase, showed negligible gold particle density when incubated with gold-conjugated rabbit IgG. Thus, under the present experimental conditions, an aspecific labeling of elastin is unlikely. This study indicates that MLE may be one of the factors responsible for the rapid development of emphysema in Tsk mice.