Elastase and papain inhibition by serum of mammals

Abstract

The protease-antiprotease imbalance concept has gained wide acceptance in reference to experimental animal models of human pulmonary emphysema. The destructive process may be induced by proteolytic enzymes such as porcine pancreas elastase (E) or papain (P), or by oxidants such as chloramine T (CT) which cause inactivation of α-1-antiprotease. The susceptibility to development of severe emphysema has been found to differ among animal species. We investigated the inhibition of elastase and papain by serum of seven species (rat, dog, human, rabbit, sheep, hamster, mini pig) and the effect of CT on serum inhibition. The relative inhibitor concentration of serum was expressed in terms of its inhibitor capacity for elastase and papain (EIC and PIC) defined as number of inhibited units (U) of enzyme catalysed hydrolysis of chromogenic peptide substrate (SAPNA and BAPNA) per unit of serum. The effect of CT on enzyme inhibition was quantified in terms of fractional loss of inhibition relative to control. The serum concentration of inhibitor was highest in the rat (EIC 8642±989 μ/μl, PIC 214.2± 110.3 μ/μl; means±SD). Next in order of decreasing EICs were dog, human, rabbit, sheep, hamster, and mini pig exhibiting the lowest EIC (2523±184 μU/μ1) while sheep had lowest PIC (39.6±3.5 μU/μ1). The EIC/PIC ratio varied from 20 (mini pig) to about 100. The reduction of elastase inhibition after CT exposure of serum was high (80-100%) in rat, dog, human, and hamster, moderate (40%) in mini pig and rabbit, and low (10%) in sheep. Because papain was directly affected by CT the effect of CT on papain inhibition could not be analysed. The data suggest that the intrinsic antiprotease and antioxidant screen varies among experimental animals. For the purpose of animal models of emphysema, hamster appears to be most susceptible to the progressive destruction of lung parenchyma elicited by experimental burden of proteases or oxidants.

Key Words:

• chloramine T
• chromogenic substrate
• elastase
• experimental emphysema
• inhibitor capacity
• papain
• protease-antiprotease imbalance
• serum protease inhibitor