Complement Activation by Interaction of Polyanions and Polycations

TLDR

Complement activation may be triggered by interactions between polyanions and polycations, analogous to antigen–antibody binding, potentially initiating inflammation. The depletion of complement activity by heparin–protamine interaction depends on time, temperature, pH, divalent cations, and serum concentration. Co‑administration of heparin and protamine in low amounts virtually abolishes hemolytic complement activity, predominantly depleting C1 and also C4 and C2, whereas each agent alone has little effect, indicating that their interaction strongly activates the classical complement pathway.

Abstract

Abstract Interactions of heparin and protamine in fresh human serum, in amounts far below those required for complement depletion by either agent alone, were found to induce virtually complete depletion of total hemolytic complement activity. This depletion was dependent on time, temperature, pH, divalent cations, and serum concentration. The predominant complement component hemolytic activity depleted was C1; under appropriate reaction conditions C4 and C2 were depleted as well. Equivalent amounts of heparin along induced lesser but substantial depletion of C1, potentiation of C4 and C2, and minimal depletion of C3-9, whereas equivalent amounts of protamine had no effect upon complement component activities. We conclude that interaction of heparin with protamine, like interaction of antibody with antigen, markedly enhances its ability to interact with the first component of complement and activate the classical complement pathway. It is suggested that complement activation by interactions between certain polyanions and polycations, like interactions between antigens and antibodies, may have a role in the initiation of inflammatory reactions.