The Role of Complement in the Binding and Degradation of Immunoglobulin Aggregates by Macrophages

Open Access
Publisher Website
Google Scholar
Abstract
The role of complement (C) in the processing of soluble immune complexes by guinea pig peritoneal macrophages was studied in a homologous system in vitro by using isolated stable IgG2 aggregates as a model for immune complexes. Degradation of immunoglobulin aggregates by macrophages is markedly stimulated in the presence of fresh serum, an effect that was shown to be mediated via the classical pathway of C. After treatment with serum, aggregates were isolated from the serum proteins by sucrose gradient ultracentrifugation and subsequently presented to the macrophages; it appeared that the stimulating effect was mediated via the binding of C to the aggregates and is probably therefore not due to generation of free C split products in the medium. Degradation by macrophages of serum-treated aggregates with comparable sedimentation rates increased as the concentration of the serum in which the aggregates had been incubated increased. Furthermore, a stimulated degradation of aggregates could be correlated with the ability of the aggregates to activate the C system as assessed by C4 consumption. Enhanced degradation of the aggregates was eliminated when the C receptors of the macrophages were removed by trypsin treatment before incubation with the aggregates. These results thus suggest that the effect observed is dependent on the ability of the aggregates to bind and activate C components and requires the presence of intact cellular C receptors. Experiments in which the rate of binding of the aggregates to the macrophage cell membrane was compared with the ingestion and digestion of membrane-bound aggregates showed that C increased the rate of binding but had no effect on the subsequent processing of the aggregates. These studies thus demonstrate that C plays an important role in the clearance of soluble immunoglobulin aggregates by mononuclear phagocytes.