Enhancement of C5̄6̄-Initiated Lysis by Cell-Bound C3 Fragments: Evidence for a Mechanism Independent of the Prior Binding of C5̄6̄ to C3b

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Abstract
Cell-bound C3b can reversibly bind C, activated complex of the fifth (C5) and sixth (C6) components of complement, and in this way potentiate C-initiated lysis by favoring the formation of C at the cell surface. We report here another way in which cell-bound C3 fragments can enhance C-initiated lysis, which involves C generated in the fluid phase rather than at the cell surface. Evidence for the involvement of fluid phase was obtained by use of dextran sulfate, which is known to inhibit the hemolysis of E mediated by fluid phase . Dextran sulfate strongly inhibited the formation of sites on cells bearing C4b and C3b (EAC4b3b) as well as on unmodified E when and C7 were added simultaneously to the cells. By contrast, dextran sulfate had virtually no effect on the reaction sequence involving the prior binding of C to C3b and subsequent formation of at the cell surface. Treatment of EAC4b3b with either anti-C3 Fab′ fragments or the C3b inactivator reduced but did not eliminate the enhancement of hemolysis, raising the possibilities that a C3 fragment(s) other than C3b also can enhance C-initiated lysis and/or that the enhancement is indirect without a requirement for an interaction between and the cell-bound C3 fragment itself.