276 IMMUNO-CATALYSIS 



serum protease may further be strengthened by consideration of the 

 interrelation of the following observations: 



(a) Prothrombin -j- thromboplastin -|-Ca+ + ^thrombin; 



(b) Prothrombin does not inhibit fibrinolysin, but is destroyed by it; 



(c) Thrombin has no demonstrable fibrinolytic activity and is resistant to the 

 proteolytic action of serum protease (Loomis, et al. 1947); and 



(d) Thromboplastin lacks any demonstrable trypsin-like enzymatic activity 

 (ChargafiF, 1945). 



Does thromboplastin combine with the activated serum protease 

 causing its inactivation? Does such a reaction account for the inactive 

 state of the serum lytic factor? Or does thromboplastin combine with 

 the bacterial fibrinolytic factor preventing its role of activating the 

 serum lytic factor? In this latter case the role of bacterial factor will 

 be equivalent to the action of organic solvents whereby the inhibitor 

 factor (or a lipid-like substance) is eliminated by its extraction with 

 chloroform. 



Evidence that a lipid-like substance keeps the normal serum protein- 

 ase in an inactive state is suggested by the observations of Jobling and 

 Petersen (1914). They advanced evidence that the normal antipro- 

 teinase action of serum depends on the serum lipids. They were able 

 to decrease the anti-proteolytic action of, or produce proteolytic activity 

 in serum, by extracting the lipids with fat solvents. They blocked the 

 proteolytic activity of the extracted serum by replacing the lipids. The 

 anti-proteolytic lipids contained unsaturated carbon bonds; by saturat- 

 ing the double bonds with iodine they found the lipids to have lost 

 their anti-proteolytic activity. Soaps of saturated fatty acids were found 

 to be unable to function as anti-proteolytic factor. Unsaturated soaps 

 neutralized the proteolytic activity. The unsaturated lipids (serum-anti- 

 trypsin) could be adsorbed from serum by kaolin, starch, agar, and 

 bacteria, rendering the serum proteolytically active. It is interesting to 

 note that bacteria treated with serum or oil did not adsorb serum lipids. 

 Bacteria were rendered resistant to the action of serum proteinase by 

 the adsorption of lipids. These observations would seem to supply con- 

 siderable support to the idea that streptococcal factor is combining with 

 the anti-proteolytic lipids and is thus rendering the serum proteolyti- 

 cally active. However, for another possible mechanism for the activa- 

 tion of serum the reader is referred to a suggestion which is discussed 

 further below. 



