The Reaction of Zymosan with the Properdin System in Normal and C4-Deficient Guinea Pig Serum

Abstract

Abstract On incubation with serum, zymosan (Z) combines with several serum components, collectively designated X, to form an intermediate, ZX, which is capable of activating the complement system by cleavage of components C3 and C5. We now report kinetic studies on the formation of ZX, as well as the reaction of this intermediate with purified C3 or C5, which indicate that the splitting of these complement components is mediated by two multi-unit enzyme complexes on the zymosan particles, one which acts on C3, and another which splits C5. These two enzymes share in common factor B of the properdin system, but differ in other respects. On extended incubation at 37°C they decay to a form designated ZXd by release of the factor B subunit. ZX can be regenerated from ZXd by treatment with factor B but this process is efficient only with respect to C5 cleavage, presumably because a subunit of the C3-cleaving enzyme, other than factor B, is also lost during decay at 37°C. The reaction of factor B with ZXd to yield ZX is believed to be enzymatic on the basis of its temperature-dependence and its kinetic behavior. Presumably, an enzyme on ZXd activates factor B, probably by cleavage, thus enabling it to combine with ZXd to form ZX. This process of activation and fixation of factor B is believed to be the final step in the complex series of reactions leading to formation of the C3- and C5- cleaving enzymes on zymosan particles. Evidence is also presented that the formation of these enzymes on zymosan proceeds much more rapidly in normal guinea pig serum than in C4-deficient serum, which indicates a marked accelerating effect of the early-acting complement components.