The contribution of the alternative and classical complement pathways to gonococcal killing and C3 fixation

Abstract

Properdin deficient (P—) and C2 deficient (C2D) sera were used to provide an unambiguous assessment of the contribution of the classical and the alternative pathways, respectively, to the killing of serum sensitive (SS) gonococci (Gc) and to correlate these results with C3 fixation. Killing was rapid (greater than 80% max in 10 min) and proceeded with identical kinetics in normal human serum (NHS) and P−. Killing in C2D occurred after a 10 min lag but the subsequent rate of killing was similar to that in NHS and P−. This difference was not due to a difference in antibody content among the sera and reconstitution of C2D with purified C2 restored killing to normal. The pattern of C3 fixation mirrored killing, occurring rapidly in NHS and P but slowly in C2D. The relationship between killing and C3 binding differed in the various sera. Twice as much C3 was deposited on Gc in NHS than in P− yet the kinetics and degree of killing were the same in the two sera. More (1.2 ×) C3 was fixed to Gc in C2D (via AP) at 10 min than in NHS at 5 min yet there was 1.5 log more kill in NHS. There was less C3 fixation by serum resistant (SR) than by SS Gc but the pattern of C3 binding was similar. We conclude that: Greater than 99.9% of gonococcal killing and 75% of C3 fixation to gonococci in NHS occurs via the classical pathway. Gonococcal killing and C3 fixation via the alternative pathway occurs following a delay which minimizes the contribution of this pathway to these events in NHS Although complement activation and C3 fixation are necessary for gonococcal killing, a fixed quantitative relationship between killing and C3 fixation was not apparent in the different sera Results obtained with NHS, in which both the classical and alternative pathways are intact, do not reflect an additive contribution of both pathways to either gonococcal killing or C3 fixation More C3 is fixed by serum sensitive than by serum resistant gonococci but the pattern of C3 deposition via the classical and alternative pathways to the two types of organisms is similar