Differential Modification of Elastase-Induced Emphysema in Hamsters by Trypsin

Abstract

The administration of trypsin 24 h before, admixed with, or 24 h after administration of an emphysema-inducing dose of porcine pancreatic elastase (PPE) to hamsters resulted in significantly enhanced destruction of lung tissue as evidenced by mean linear intercept values 4 weeks post PPE. The coadministration of trypsin with a nonemphysema-inducing dose of PPE resulted in a significant destructive lung lesion. Administration of trypsin 24 h before or admixed with human leukocyte elastase (HLE) resulted in a lesion that was significantly reduced relative to that produced by administration of HLE alone. When trypsin was administered 24 h after HLE, no effect on the lesion was observed. In vitro, coincubation of trypsin with PPE resulted in a slight enhancement of rate of hydrolysis of elastin, while coincubation of trypsin with HLE resulted in a significant reduction of the rate of hydrolysis. These results suggest that interaction with other proteases may offer an additional physiological control mechanism to prevent inappropriate tissue destruction.