The Dose-Dependent Fate of Enzymatically Active and Inactivated Tritiated Methylated Pancreatic Elastase Administered Intratrachealy in the Hamster1–3

Hamsters were intratracheally instilled with saline solutions containing a high dose (145 to 220 µg) or a low dose (1.3 to 1.5 µg) of 3H-methylated pancreatic elastase or N-acetyl- (l-alanyl)3-l-alanine chloromethyl ketone-inactivated 3H-methylated pancreatic elastase. Only the lysyl residues of the elastase molecule were methylated and radiolabeled in a nonlabile manner. The 3H-methylated elastase preparation exhibited esterolytic and elastolytic activity, spectral properties, and emphysema-inducing properties indistinguishable from those of unmodified pancreatic elastase. There was no detectable hemorrhagic or emphysematous reaction with the inactivated 3H-methylated elastase, and this material was cleared from the lungs 11 times faster than the corresponding enzymatically active high dose of 3H-methylated elastase and 18 times faster than the corresponding enzymatically active low dose of 3H-methylated elastase. There were correspondingly higher amounts of radioactivity in the urine of hamsters treated...