Studies on the inhibition of C56 initiated lysis (reactive lysis). I. Description of the phenomenon and methods of assay.

Reactive lysis refers to the lysis of unsensitized cells by late acting complement components (C5—C9) acting independently of early components. The existence in human serum of an activity which inhibits reactive lysis had been inferred previously from certain morphological features of the reactive lysis of red cells suspended in agarose gels, and from the difficulty with which reactive lysis proceeds in whole serum. We have found this activity, which we abbreviate `INH-RL', in all human sera tested, and in the serum of several experimental animals. We have developed two methods of detection of INH-RL in gels, and have established a sensitive, quantitative assay for INH-RL in solution, which has been adapted to the measurement of INH-RL in serum. We have examined the effect of INH-RL on the measurement of C[unk]56 and C7 by reactive lysis in gels. Inhibition of distal complement components in primary lysis of EAC[unk]142 by INH-RL was detectable but was markedly less potent than inhibition of reactive lysis. INH-RL is distinct from other known complement inhibitors, and thus represents a newly appreciated regulatory mechanism in the complement cascade. It may have importance in quenching the indiscriminate haemolytic activity which can be generated from complement in the fluid phase, especially by stimulation of the alternative pathway.