The Derivation of Two Distinct Anaphylatoxin

The relationship of anaphylatoxin to the complement system has received increasing attention in the past few years. Osier et al. (1) observed a positive correlation between the activity of the third component of complement in rat serum and the capacity of the serum to generate anaphylatoxin. Recently, a direct relation of anaphylatoxin with the complement system has been demonstrated through the use of purified components of complement. Dias da Silva and Lepow (2) have presented clear evidence that an agent with the full spectrum of anaphylatoxin activities is dissociated from C"3 on interaction of Crl esterase with C'2, C'3, and C'4 in free solution. When C'5 was added to this system, anaphylatoxin activity was neither augmented nor diminished, suggesting that C'5 was not essential for anaphylatoxin formation. In contrast to these findings, Jensen (3), working with functionally purified complement components of guinea pig serum, related anaphylatoxin activity to C'5, and not to C'3. This conclusion was drawn primarily from experiments in which anaphylatoxin was generated by treatment of functionally purified Ct5 either with trypsin or EAC'la, 4, 2a, 3, or with an anticomplementary factor of cobra venom. In view of these disparate conclusions as to the identity of anaphylatoxinogen in the guinea pig and human complement systems, we undertook experiments to examine if C~5 as well as C"3 could serve as parent molecules of anaphylatoxin. Advantage was taken of the availability of highly purified components of human complement in this laboratory and of the possibility of introducing a radioactive label into these proteins. In addition, use was made of an anti-