Ultrastructural changes in hamster lung 15 min to 3 hr after exposure to pancreatic elastase

A single endotracheal instillation of porcine pancreatic elastase into hamster lungs induces morphological changes that can be detected as early as 15 min after the instillation of enzyme. Lung tissue from animals sacrificed at six time points between 15 min and 3 hr after enzyme instillation was examined for ultrastructural alterations. There were few of these alterations and they were highly focal, but they included damaged epithelial cells and partially digested elastic fibers that occurred both in the parenchyma and the pleura. A cytochemical technique employing N-t-Boc-L-alanine-p-nitrothiophenyl ester as a substrate for elastase-like enzymes was also used in an effort to locate pancreatic elastase shortly after instillation into the lungs. Reaction product was observed on the alveolar surface and in pinocytotic vesicles of alveolar type I cells, in connective tissue areas, in fibroblasts, and in pinocytotic vesicles of capillary endothelial cells. The location of reaction product coupled with ultrastructural alterations in the tissue suggests that pancreatic elastase instilled into the trachea may reach the interstitium in two ways: First, transport may take place across intact alveolar type I cells via pinocytotic vesicles, and second, a small amount of enzyme may gain access to the connective tissue after the disruption of epithelium in a few highly focal areas.