Enzymatic Hydrolysis of Benzoylarginineamide by Normal and Tuberculous Tissue of Rabbits. ∗

Abstract

Summary and Conclusions

1. Caseous material was produced in the lungs and kidneys of rabbits by intratracheal infection with a virulent, Ravenel culture of tubercle bacilli. The animals were killed at intervals of from 5 to 20 weeks after infection. The lungs and kidneys, together with the livers and spleens, were removed immediately after exsanguination and death of the animals, preserved at a very low temperature in a dry ice refrigerator, and examined for enzymatic activity.

2. Homogenates of tuberculous lung tissue containing very large amounts of caseous material can hydrolyze benzoylarginineamide (BAA) at pH 5.1 at a more rapid rate than those of homologous normal tissues. The lungs and kidneys of animals which were first immunized with a non-virulent culture before reinfection with a virulent strain of M. tuberculosis were found to have greater enzymatic activity than those with a primary infection.

3. These results are analogous to those of Lurie who showed an increased capacity of rabbit tissue to destroy virulent tubercle bacilli under similar circumstances. They are also of interest since we have previously demonstrated 9 a parallelism between bactericidal action and the rate of hydrolysis of BAA in innate organ immunity.

4. It is not clear whether the observed increased rate of enzymatic activity has its origin in the caseous (“necrotic”) material itself or in the surrounding inflammatory exudate (“granulomatous tissue”). The following hypothesis is suggested: The lungs and kidneys of rabbits possess little innate resistance to infection with virulent tubercle bacilli. Hence the latter multiply freely and bring about an inflammatory exudate which is the source of the added enzyme. The liver and spleen, on the other hand, are organs of high natural immunity. They do not permit rapid multiplication of tubercle bacilli (Lurie²). The intense inflammatory response with enzyme-laden cells is therefore not called forth.

5. The decreased rate in BA-amidase activity observed in liver homogenates after primary and reinfection, may perhaps be due to the loss of labile liver protein which occurs during the malnutrition accompanying the late stages of a virulent tuberculous infection.