Effects of C1̄ on the Size of Soluble Immune Aggregates and on Their Processing by Macrophages

Abstract

Abstract The effect of isolated C1̄, the first component of complement (C), on the processing of soluble IgG aggregates by mononuclear phagocytes was studied in vitro with a homologous guinea pig system and isolated stable IgG2 aggregates. The interaction of C1̄ with IgG2 aggregates was demonstrated by the inhibition of functional C1̄ hemolytic activity and was shown to be dependent upon the number of IgG2 molecules per aggregate. Analysis of the interaction of C1̄ with the soluble aggregates by ultracentrifugation on sucrose gradients revealed dissociation of aggregates into smaller aggregates and monomeric immunoglobulin molecules. As a consequence of this effect the processing of C1̄-treated aggregates by peritoneal macrophages or Kupffer cells was significantly decreased compared to aggregates not treated with C1̄. The decreased processing was shown to be due to an inhibited binding of the dissociated aggregates to the cells. When the aggregates were incubated with macrophages in various concentrations of fresh serum containing isolated C1̄, the inhibitory effect of C1̄ was overcome and a stimulated degradation was seen, depending upon the ratio of C1̄ to the other serum proteins. On the other hand, when aggregates had been preincubated with C1̄, subsequent addition of fresh serum could not reverse the inhibitory effect. Although competition between C1̄ and Fc receptors for the Fc parts in the immune aggregates may explain the inhibitory effect of C1̄ on the degradation of soluble immune aggregates by macrophages, dissociation of these aggregates by C1̄ is the major mechanism involved.