PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 437 



Liberation of histamine by the action of snake and bee venoms on 

 egg yolk lecithin with the formation of lysolecithin which per se is 

 capable of liberating histamine has been shown (Feldberg and Kel- 

 laway, 1938). Trethewie (1939) showed that the hemolytic activity 

 of venoms parallels their histamine liberating capacity. Rocha e Silva 

 (1941) expressed the opinion that the whole picture of histamine 

 liberation could be related to the proteolytic activity of venoms. 

 Histamine could be released from the lipoprotein films of the proto- 

 plasmic structure of cells by the action of lysolecithin on the lipid 

 component, and by the action of proteolytic enzyme on the protein 

 component. Digestion of the protein would lead to a destruction of the 

 normal lipoprotein structure with the consequent release of histamine 

 (Feldberg, 1941). According to Rocha e Silva (1941), in this respect 

 venoms and trypsin are indistinguishable. Proteolytic liberation of 

 histamine as the cause of anaphylactic and tryptic shocks, and certain 

 fatal symptomatologies of snake and bee venom action constitutes a 

 central feature of the views of Rocha e Silva (1944). After brief 

 reference to the older literature with respect to the appearance of 

 products of enzymatic splitting of proteins in the circulating blood 

 of sensitized animals submitted to shock, in support of this theory, he 

 makes the following quotation from Vaughan (1913): "We hold that 

 sensitization develops in certain body cells a new function— that of 

 elaborating a new specific, proteoclastic ferment." 



The liberation of histamine in anaphylactic shock is attributed to 

 the activation of cellular cathepsins. Cathepsin is a proteolytic enzyme 

 of animal tissues and belongs, according to the Bergmann scheme, to 

 the class of proteinases consisting of trypsin, papain-H^S and cathepsin 

 II. These require lysine and arginine in the peptide-chain such as 

 benzoyl-1-arginine amide and benzoylglycyl-1-lysine amide for sub- 

 strates (Bergmann and Fruton, 1941; Fruton, Irving and Bergmann, 

 1941). Rocha e Silva is inclined to believe that histamine is bound to 

 cells forming peptide bonds with the amino acid chain of tissue pro- 

 teins. This peptide bond displays a definite specificity toward pro- 

 teolytic enzymes which split the amide groups from the above men- 

 tioned type of peptide chain substrates. Chymotrypsin which does not 

 split these substrates is practically devoid of the capacity of liberating 

 free, active histamine from cells. On the other hand, a fractionation 

 of papain has yielded a preparation whose ability to liberate histamine 



