ORIGIN OF COMPLEMENT 79 



Origin of Complement. Regarding the origin of the complement, 

 Buchner and Metschnikoff both thought that it was derived from 

 the leukocytes, but while Buchner looked upon the substance as a 

 secretory product of the living cells, Metschnikoff claimed that com- 

 plement is only formed when the cell dies, during the process of 

 blood coagulation; and that it does not exist preformed in the circu- 

 lating blood. An enormous amount of labor has been expended to 

 support this view of Metschnikoff on the one hand and to disprove 

 it on the other. As a result it may now be regarded as a fairly well 

 established fact that the normal body fluids contain free complement 

 even when there is no evidence that leukocytic degeneration has 

 taken place. 



The long-discussed question, also, whether or not the blood-plasma 

 contains free complement, may now be answered in the affirmative. 

 On the other hand, there can be no doubt that bactericidal substances 

 can be extracted directly from the leukocytes. This can be shown 

 in the following manner: An aseptic exudate is produced in animals 

 by the intrapleural injection of aleuronat, when the cellular elements, 

 which are mostly polynuclear leukocytes (Metschnikoff's micro- 

 phages), are thoroughly washed with saline, repeatedly frozen and 

 thawed and the resultant material allowed to stand at body tem- 

 perature. After a while it can then be shown that this extract is 

 quite rich in bactericidal substances, and like the fresh blood-serum, 

 loses its action on exposure to higher temperatures. But on com- 

 paring the behavior of such leukocytic extracts with normal bacteri- 

 cidal sera certain points of difference appear, nevertheless, which 

 suggest that the substances which are operative on the two sides 

 may not be identical. 



Apart from the different temperature at which inactivation takes 

 place and the slower action of the leukocytic extracts which, more- 

 over, can progress in the absence of neutral salts (contrary to the 

 bacteriolytic sera), it is especially noteworthy that certain organ- 

 isms, such as the cholera vibrio and the typhoid bacillus, which are 

 very susceptible to the action of bacteriolysins, are hardly affected 

 by leukocytic extracts. The latter, moreover, contain no substances 

 which are capable of activating inactivated anticholera or anti- 

 typhoid sera, i. e., sera containing the corresponding bacteriolytic 

 amboceptors, but deprived of their active complement. 



We are thus forced to conclude that the leukocytic origin of com- 



