PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 433 



The liberation and the role of proteolytic enzyme before or during 

 anaphylactic shock, or any kind of shock, as a cause of these processes 

 has been claimed and refuted for over four decades. It has been oft 

 claimed that shocks are preceded by the liberation of proteases which 

 produce peptone-like digestion products which, as discussed above, 

 produce characteristic anaphylactic symptoms. The fact, however, 

 that the reinjection of microgram quantities of an antigen into a 

 sensitized animal is capable of producing almost an immediate shock 

 has been advanced as an argument against the "proteolytic enzyme" 

 mechanism of anaphylactic shock. It is argued that a few minutes' time 

 interval preceding shocks of sudden and explosive nature is too short 

 a period to liberate proteases capable of producing an adequate amount 

 of toxic peptone-like digestion products. It is difficult to state at present 

 to what extent one can place sufficient weight on such arguments. 

 We are in the dark concerning the relative speed and quantitative 

 relationship between the proteolytic processes occurring in vivo and in 

 vitro. Almost nothing is known about the possible speed of chemical 

 reactions within the organism and of the mechanisms involved. 



One may perhaps make reference to an observation by Jacobson 

 (1947). He reported two hitherto unrecognized chymotrypsins, one of 

 which was from 2 to 2.5 fold, and the other 1.5 fold more active than 

 the ordinary chymotrypsin. It is not at all impossible that in animal 

 systems the native proteolytic enzymes are far more active than they 

 are in an artificial environment. In connection with the role of 

 proteolytic enzymes in shock, it may be of interest to refer to the studies 

 of Jobling and Petersen (1914a, 1914b, 1914c). After a review of 

 older findings concerning the inhibitory role of lipids on the proteolytic 

 activity of serum proteases, they reported that antitrypsin activity of 

 serum is due to the presence of compounds of unsaturated fatty acids. 

 The sera from which these protective lipids have been removed by 

 various means were rendered toxic for the homologous animal. The 

 toxicity is due to (a) an alteration in the mechanism of clotting, 

 with resulting intravascular clotting; (b) the exposure of the native 

 serum proteins; and (c) the formation of toxic split products (primary 

 proteases) by digestion. The return of the extracted lipids neutralizes 

 the toxicity of sera. The toxicity of the extracted serum is the result 

 of the serum protein digestion products rapidly produced by serum 

 proteases freed from the inhibiting action of serum lipids. Anaphyla- 



