The role of complement in the processing of soluble immune complexes by guinea-pig peritoneal macrophages was studied in an homologous system in vitro by using immune complexes prepared with bovine thyroglobulin as the antigen and guinea-pig IgG2 antibodies. The simplest complexes showing complement activation and which were degradable by macrophages had a composition of Ag1 Ab2-3. Complement was shown to have an enhancing effect on the degradation of complexes which had an antibody: antigen ratio in the complexes which was at least 4 (Ag1 Ab4). The effect of size on complement activation and degradation of the complexes by macrophages was studied by employing the observation that immune complexes increase in size during their preparation. In the presence of serum as a complement source it was shown that degradation of small complexes by macrophages was inhibited whereas the degradation of large complexes was enhanced. The enhanced degradation of complexes in the presence of fresh serum did not occur in C4-deficient serum nor in EDTA-serum, which indicates that the observed effect is complement mediated. The experiments described here thus extend and confirm earlier studies using heat aggregated immunoglobulins and show that complement may play an important role in the elimination of immune complexes in vivo.
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