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The cytolytic C5b-9 complement complex: feedback inhibition of complement activation.

S Bhakdi·F Maillet·M Muhly·M D Kazatchkine
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Abstract

We describe a regulatory function of the terminal cytolytic C5b-9 complex [C5b-9(m)] of human complement. Purified C5b-9(m) complexes isolated from target membranes, whether in solution or bound to liposomes, inhibited lysis of sensitized sheep erythrocytes by whole human serum in a dose-dependent manner. C9 was not required for the inhibitory function since C5b-7 and C5b-8 complexes isolated from membranes were also effective. No effect was found with the cytolytically inactive, fluid-phase SC5b-9 complex. However, tryptic modification of SC5b-9 conferred an inhibitory capacity to the complex, due probably to partial removal of the S protein. Experiments using purified components demonstrated that C5b-9(m) exerts a regulatory effect on the formation of the classical- and alternative-pathway C3 convertases and on the utilization of C5 by cell-bound C5 convertases. C5b-9(m) complexes were unable to inhibit the lysis of cells bearing C5b-7(m) by C8 and C9. Addition of C5b-9(m) to whole human serum abolished its bactericidal effect on the serum-sensitive Escherichia coli K-12 strain W 3110 and suppressed its hemolytic function on antibody-sensitized, autologous erythrocytes. Feedback inhibition by C5b-9(m) represents a biologically relevant mechanism through which complement may autoregulate its effector functions.

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Complement ActivationComplement C3-C5 ConvertasesComplement Membrane Attack ComplexComplement Pathway, AlternativeComplement Pathway, ClassicalComplement System ProteinsHumansJournal ArticleResearch Support, Non-U.S. Gov't

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BibTeXRIS

S Bhakdi, F Maillet, M Muhly, M D Kazatchkine. 1988. The cytolytic C5b-9 complement complex: feedback inhibition of complement activation.. https://doi.org/10.1073/pnas.85.6.1912

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