322 IMMUNO-CATALYSIS 



lowing the hemolysis of erythrocytes and the liberation of certain 

 reaction products, may be comparable to the inhibition of amylase by 

 /3-maltose as a hydrolytic product of starch. 



The substrate for hemolysin according to this interpretation is the 

 red cell proper. The function of hemolysin as catalyst is to disorganize 

 the highly organized cell, and it does this without being inhibited 

 during the process of hemolysis by the "inhibitors" present in the 

 intact cell. The inhibitors, believed to be cholesterol (and lipids), are 

 liberated as a result of catalytic disorganization of the cell. 



The combination between the hemolysin and cholesterol (one 

 H.U.=3 to 9X10-^ mg. N and 1.5X10-^ mg. of cholesterol, Cohen, 

 et al. 1940) does not appear to produce chemical changes in their 

 constitution. For, the combination cholesterol-lysin, extracted during 

 the most rapid and effective stage of union by benzol, yields a product 

 which is actively hemolytic again (recovery from 1 to 16 per cent). 

 These investigators stated that "Despite the low recoveries, it seems 

 significant that the inactivating cholesterol is removable by simple 

 extraction." These findings show that the stoichiometrical inactivation 

 of lysin by cholesterol is not due to an irreversible chemical degrada- 

 tion of the reactants. This type of inactivation by cholesterol is the com- 

 mon characteristic of inhibitors produced during a reaction catalyzed 

 by an enzyme.* 



*Bemheimer and Cantoni (1945) reported that the preparation containing oxygen- 

 labile hemolysin of Stre'ptococcus pyogenes induces systolic contracture, the contrac- 

 ture usually developing only after the second of two administrations of the prepara- 

 tions. A single application of the streptococcal preparation sensitized the heart to a 

 second application. The cardiotoxic factor was found to be identical with the oxygen- 

 labile hemolysin of streptococci. The capacity of normal and of immune sera to 

 neutralize the cardiotoxic action paralleled the antihemolytic potency of the sera. 

 Cantoni and Bemheimer (1945) found that the sensitization depends upon the 

 release from the isolated heart of a substance which inhibits the action of the cardio- 

 toxin. The inhibitor is released upon the first (sensitizing) administration of cardio- 

 toxin, but not upon the second (contracturing) administration. The released inhibitor 

 neutralizes the lethal factor present in the streptococcal preparation employed. The 

 inhibitor is thermostable, 10 minutes at 70°C. chloroform-soluble and non-dialyzable, 

 which may suggest that it is a lipid-like substance, or cholesterol. Hewitt and Todd 

 (1939) made the observation that, in the absence of protein, streptolysin S is power- 

 fully inhibited by lecithin. Humphry (1949) reports that anti-streptolysin S is not 

 an antibody in the accepted sense, and its nature varies between species, and even 

 between individuals. He described two types of antistreptolysin S. One: Lipoprotein 

 loose complexes represented by (a) materials extractable (thus removing inhibitory 

 activity) with ether, and (b) stable lipoprotein complexes, the activity of which are 

 removed by ether after digestion of denatured material. Two: Non-specific proteins, 

 the activity of which is destroyed by prolonged peptic digestion. 



