DEFENSE AGAINST AUTOLYSIS 83 



the spleen contains an enzyme digest inj!; in alkaline solution," and 

 another which acts best in weak acids, the latter appears more 

 proniinontly under ordinary conditions because the spleen and the 

 blood contain antibodies which check the enzyme that acts in alka- 

 line solutions, while acids destroy this antibody (Hedin).^^ Organic 

 acids are formed in autolysis of the tissues, and the latent period be- 

 tween the time of the removal of an organ from the body and the ap- 

 pearance of autolysis may be explained partly by the time recjuired 

 for the neutralization or alkalinity. Bradley'^ has also obtained evi- 

 dence that the acid renders the substrate susceptible to digestion by the 

 proteases. Dernby's^^ demonstration of the existence of pepsin-like 

 and erepsin-like enzymes suggests that there must be developed 

 enough acidity to permit the peptase to form peptones before the 

 ereptases can begin their further cleavage. Maximum autolysis is 

 known to occur when tissues are first made acid and then neutralized 

 or slightly alkalinized (Hedin) . The old observation that rigor mortis 

 disappears most rapidly in muscles that have been exhausted just 

 before death is probably explained by the greater amount of acid in 

 such muscles. If we imagine that autolysis is limited to periods 

 when the cells have an acid reaction, however, we limit the range of 

 usefulness in the living cell to a minimum, since during life the tissue 

 fluids, and presumably the cell contents, are preponderatingly alka- 

 line. The control of autolysis by maintenance of a low H-ion concen- 

 tration is undoubtedly an important factor, for Bradley found that a 

 reaction equal to that of blood almost completely inhibits autolysis, 

 while the degree of increased H-ion concentration that may develop in 

 local asph3^xia, or after death, produces optimum conditions for 

 autolysis. 



Still another possible defense of the Hving cells may be found in 

 the existence of specific antienzymes. Just as the serum contains anti- 

 trypsin, so it seems to contain substances antagonistic to the autolytic 

 enzymes. Levene and Stookey found that tissue juices show a resist- 

 ance to digestion, Yamakawa^^ found that serum autolysis is prevented 

 by an antienzyme, and Opie found that the serum of inflammatory 

 exudates retards the action of the autolytic enzymes that are con- 

 tained within the leucocytes. Serum also inhibits autolysis of the 

 tissues, so it is probable that continuance of the circulation may pro- 

 vide antibodies to the tissues to hold the intracellular enzymes in 

 check, possibly without interfering with their action on other pro- 

 teins than those of the cell structure.''* (See Antienzymes.) It is 



^2 Morse (Jour. Biol. Chem., 1917 (31), 303) considers this enzyme to be heter- 

 olj'tic, derived from the white cells. 



" Festschrift f. Hammarsten, Upsala, 1906. 



'••According to Guggenheimer (Deut. Arch. khn. Med., 1913 (112), 248; Dent, 

 med. Woch., 1914 (40), 63),- the serum in various diseases has a characteristic 

 stimulating or inhibiting effect on in vitro tissue autolj'sis, but the conditions of 

 such experiments are so complex as to make their significance doubtful. 



