Effects of soluble aggregates of IgG on the binding, uptake and degradation of the Clq subcomponent of complement by adherent guinea pig peritoneal macrophages

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Abstract
Earlier studies have indicated that Clq, the first subcomponent of complement component C1, is bound to lymphocytes via specific Clq receptor sites. We have recently shown that adherent guinea pig peritoneal exudate macrophages express specific receptors for Clq (Veerhuis, R. et al., Immunology 1985. 54: 801). The present studies were performed to determine whether binding of 125I-labeled human Clq (125I-Clqhu) to adherent guinea pig peritoneal exudate macrophages would also result in ingestion and subsequent degradation of 125I-Clqhu. The binding of 125I-Clqhu to adherent peritoneal macrophages at 4°C is inhibited fully not only by Clqhu and guinea pig Clq (Clqgp) but also by pepsin fragments of Clqhu. The amount of trichlo-roacetic acid nonprecipitable radioactivity that appeared in the supernatant was used as a measure for the degradation of 125I-Clqhu. 125I-Clqhu is degraded initially into fragments of 25 kDa, after which it is degraded further into small molecular weight peptides. Ingestion of 125I-Clq by the macrophages occurs before the 125I-Clq is degraded. In the presence of limited amounts of soluble aggregates of guinea pig IgG2 (AIgG), a known activator of C1, part of the Clq is bound to the AIgG and all of the AIgG in turn is bound to the cellular Fc receptors leading to an enhanced binding of 125I -Clq to the cells, a binding that was maximal at near equimolar concentrations of 125I-Clqhuand 131I-AIgG. In the presence of a 30-fold excess of AIgG, however, only a small percentage of the AIgG binds to cellular Fc receptors and the interaction of Clq with its receptor is decreased due to competitive inhibition. The results presented in this report thus suggest that free Clq may be eliminated by specific interaction with Clq receptors present on circulating and tissue phagocytoses and, in addition, that in the presence of immune complexes modulation of elimination of Clq may be encountered.