ANTI-ENZYME IMMUNITY 247 



Guerra (1946) reported that sodium salicylate inhibited the spreading 

 eflFect of hyaluronidase. In a total of 96 experiments on 24 albino 

 rabbits, he observed that the spread area of India ink with hyaluroni- 

 dase was six times greater than with saline. The oral or intravenous 

 administration of sodium salicylate inhibited by 57 to 66 per cent the 

 spreading effect of hyaluronidase; the degree of inhibition varied with 

 the dose of salicylate administered. He concluded that the evidence 

 found in normal rabbits and humans, as well as in individuals who 

 have latent or active rheumatic fever, indicates the important role of 

 hyaluronidase in its mechanism and the inhibitory effect of sodium 

 salicylate as a typical antirheumatic drug. Meyer (1947) reported that 

 in in vitro experiments equivalent or higher concentrations of salicylate 

 are without effect on the depolymerization or hydrolysis of hyaluronate, 

 but the permeability of rabbit skin was depressed by the action of 

 salicylate. 



In a series of three papers, Haas (1946) reported that normal plasma 

 contains a non-specific, highly active enzyme (anti-invasin I, using the 

 term invasin for hyaluronidase) which rapidly destroys hyaluronidase. 

 He reported also a proinvasin I which is found in bacteria and venoms 

 which rapidly inactivates antinvasin I. On the other hand, normal 

 plasma contains an antinvasin II which destroys proinvasin I, and 

 thereby indirectly counterracts invasion. He reported a number of other 

 enzyme factors interfering with one or the other above reactions. 

 Dorfman, et al. (1947) investigated the claims of Haas and found that 

 the reaction between hyaluronidase and antinvasin I is virtually com- 

 plete in three minutes despite the presence of unreacted hyaluronidase. 

 They suggested that this reaction is not enzymatic in nature, but that 

 it is due to an inhibitor of protein nature (Dorfman, et al., 1948). 

 Meyer (1947) declined to agree with Haas' claims for experimental 

 reasons and considered the results of Haas as due to competitive re- 

 actions between various proteins among themselves and for the acid 

 substrate. The reaction involved in the development of the turbido- 

 metric method by Kass and Seastone (1944) are somewhat confirma- 

 tory of Meyer's suggestion. In a recent note, Goldberg and Haas (1947) 

 reported that his anti-hyaluronidase is a serum protein consisting of heat 

 labile and thermostable components; neither of them is active singly. 



b. Neutralization of Hyaluronidase or the Permeability Factor by 

 Specific Immune Serum. Most of this work was performed by Mc- 



