Inhibition of C5 convertase by epsilon amino caproic acid (EACA): a limiting factor in the generation of C5a anaphylatoxin.

The effect of EACA on spontaneous C5 consumption and on the mechanisms of C5 activation through the alternative pathway of complement were analyzed. In contrast to the effect upon C3, ADDITION OF 1 M EACA to normal human serum (NHS) did not enhance spontaneous consumption of C5, but augmented its haemolytic efficiency. In the presence of 1 M EACA, activation of serum with zymosan (Z), resulted in inhibition of the formation of C5 convertase, and thus of C5 cleavage and C5a anaphylatoxin release. The generation of a C5 convertase on activated zymosan (Z) was inhibited when Z was formed at 17 degrees with NHS containing 1 M EACA. In contrast, if Z was formed in the absence of EACA the C5 convertase could be regenerated with fresh serum containing 1M EACA. Nearly maximal C5 consumption was obtained if 5 mM EGTA and 10 mM MgCl2 were added to the mixture. These conditions are considered optimal for generation and maximum recovery of fully active anaphylatoxin.