Relationship Between Elastolytic Activity and Experimental Emphysema-Inducing Properties of Papain Preparations1,2

Abstract

Amorphous and crystalline papain were administered endotracheally to hamsters, and the severity of resulting emphysema was estimated by measurement of the mean linear intercept. Crystalline papain was 5.8 times more potent, per unit weight, in inducing emphysema than the amorphous papain. In vitro studies showed that the ratio of activity, per unit weight, of crystalline to amorphous papain in hydrolyzing benzoyl arginine ethyl ester was 22.7, thus greatly overestimating the relative emphysema-inducing activity of crystalline papain. The ratio of crystalline to amorphous papain activity against t-butyloxycaronyl-l-alanine-p-nitrophenyl ester, an artificial substrate for elastase of pancreatic and other origin, was 1.3, underestimating relative emphysema-inducing activity of crystalline papain. However, the ratio of crystalline to amorphous papain in solubilizing bovine elastin was 6.4, closely paralleling the emphysema-inducing properties of the two enzyme preparations. These data support the emerging concept that elastin fibers are the major connective tissue element attacked in enzyme-induced experimental emphysema. They also suggest that in studies of this model, naturally occurring elastin rather than synthetic substances should be used as substrate when relating in vitro enzymatic activity to in vivo emphysema-inducing properties.