STUDIES ON FATE OF PANCREATIC ELASTASE IN HAMSTER LUNG - GUANIDINATED-C-14 ELASTASE

Abstract

Intratracheal instillation of pancreatic elastase in hamsters produces emphysema which progresses up to 1 yr after the insult. A guanidinated derivative of porcine pancreatic elastase labeled with 14C 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 h after intratracheal instillation of the [14C]guanidinated elastase, the whole lung retained only 40% of instilled radioactivity, but after 96 h 1% was still present. At 2 h approximately 90% of the radioactivity in the lungs could be removed by bronchopulmonary lavage, and at 96 h, 28% was removable by this method. More than half of radiolabeled elastase recovered in the lavage fluid at 2 h was enzymatically active; enzymatic activity diminished to very small amounts by 96 h. The long-term binding of active elastase to lung tissue may be involved in the progressive nature of elastase-induced emphysema.