Studies on the fate of pancreatic elastase in the hamster lung: 14C-guanidinated elastase

Abstract

Intratracheal instillation of pancreatic elastase in hamsters produces emphysema, which progresses for up to one year after the insult. To study this process in more detail, a guanidinated derivative of porcine pancreatic elastase labeled with carbon-14 was prepared that was indistinguishable from unmodified elastase with respect to physicochemical properties and in vitro enzymatic activity. Guanidinated pancreatic elastase exhibits the same emphysema-inducing potency as unmodified pancreatic elastase. Two hours after intratracheal instillation of the [14C] guanidinated elastase, the whole lung retained only 40 per cent of the instilled radioactivity, but after 96 hours one per cent was still present. At 2 hours approximately 90 per cent of the radioactivity in the lungs could be removed by bronchopulmonary lavage, and at 96 hours 28 per cent was removable by this method. More than half of the radiolabeled elastase recovered in the lavage fluid at 2 hours was enzymatically active; enzymatic activity diminished to very small amounts by 96 hours. These data support the concept of the long-term binding of active elastase to lung tissue, a phenomenon that may be involved in the progressive nature of elastase-induced emphysema.