Effects of soluble aggregates of IgG on the binding, uptake and degradation of the Clq subcomponent of complement by adherent guinea pig peritoneal macrophages
✍ Scribed by Robert Veerhuis; Leendert A. van Es; Mohamed R. Daha
- Publisher
- John Wiley and Sons
- Year
- 1985
- Tongue
- English
- Weight
- 806 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Earlier studies have indicated that Clq, the first subcomponent of complement component C1, is bound to lymphocytes via specific C l q 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 12'I-labeled human C l q (12' 1- Clqh") to adherent guinea pig peritoneal exudate macrophages would also result in ingestion and subsequent degradation of lz'I-Clqh". The binding of "'I-ClqhU to adherent peritoneal macrophages at 4°C is inhibited fully not only by Clqh" and guinea pig Clq (Clqgp) but also by pepsin fragments of Clqh". The amount of trichloroacetic acid nonprecipitable radioactivity that appeared in the supernatant was used as a measure for the degradation of "'I-Clqh". 1251-Clqh" is degraded initially into fragments of 25 kDa, after which it is degraded further into small molecular weight peptides. Ingestion of 12'I-Clq by the macrophages occurs before the 12'I-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 ' ' ' 1 -Clq to the cells, a binding that was maximal at near equimolar concentrations of 12'I-Clqh" and 1311-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 C l q 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 C l q receptors present on circulating and tissue phagocytoses and, in addition, that in the presence of immune complexes modulation of elimination of C l q may be encountered.