Elastase-induced emphysema: asynchronous bronchial, alveolar and endothelial cell proliferation during the acute...

This study was undertaken to determine whether elastase injury, which results in extensive remodelling of the hamster lung to produce a panacinar type of emphysema, also induces significant lung cell damage. Anaesthetised hamsters were given a single intratracheal injection of 0.3 mg (18 units) purified elastase (Sigma Type IV) in physiologic saline and were killed 4, 6, 8, 16, 24 h, 2, 4, 8, and 16 days after exposure. DNA synthesis was assessed by autoradiography of sectioned tissue and scintillation counting of tissue blocks using injected tritiated thymidine (3HTdR). DNA, RNA and protein levels were also measured. Saline injected and unexposed animals were used as controls. Widespread mitotic activity was induced in three separate cell compartments, the peak of activity in each compartment occurring at different times. The first peak in labelling index was seen in non-ciliated, non-secretory bronchial cells at 24 h when a value of 8 per cent was reached. This was followed by mitosis in Type II alveolar cells with a labelling index of 15 per cent at 2 days and, lastly, in endothelial cells which showed an index of 9.8 per cent at 4 days. The differences between the peaks was significant (P less than 0.001). RNA content on elastase-exposed animals showed prolonged depression and had not regained control values by the end of the experiment. Protein and DNA content, and 3HTdR incorporation showed significant elevations, particularly about the fourth day after injury. Protein and DNA content and 3HTdR incorporation were not significantly changed in either group of controls.