Elastase-induced emphysema: Asynchronous bronchial, alveolar and endothelial cell proliferation during the acute response to injury

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Abstract
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 phsiologic 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 cell at 24 h when a value of 8 per cent. was reached. This was followed by mitosis in Type II alveolar cell 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 ≤ 0.001). RNA content in 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. The study shows that there is asynchronous mitotic activity in bronchial, alveolar Type II epithelial, and endothelial cells following a dose of elastase which is known to induce emphysema. More important, it shows that the lung reaction to elastase is quite different from the response induced by oxygen, ozone, nitrogen dioxide and cadmium chloride injuries, where the injury is predominantly epithelial. In contrast, we believe that elastase damages the structural framework of the lung and that this indirectly stimulates mitotic activity in the cells lining airways and blood vessels.