The role of cellular Fc and C3 receptors on the complement-dependent degradation of stable soluble immunoglobulin aggregates by normal and trypsin-treated peritoneal macrophages.
The experiments described in this paper were designed to determine the degradation of soluble IgG aggregates (AIgG) bearing C3b by guinea-pig peritoneal macrophages with different numbers of functional C3b receptors. The number of functional Fc receptors for AIgG containing 40 molecules of IgG per aggregate (AIgG40) were kept constant during these experiments. By increasing the concentration of trypsin for the treatment of normal peritoneal macrophages a dose-dependent inactivation of C3b receptors was achieved as determined by the binding of tetrameric [125I]-C3b([125I]-AC3b). Normal peritoneal macrophages bound 148,500 AIgG40 and 60,300 AC3b per cell. Treatment of the macrophages for 15 min at 37 degrees with incremental amounts of trypsin from 60 to 1000 micrograms/ml did not affect the binding of AIgG40 to macrophages but caused a dose-related loss of up to 95% of AC3b binding, indicating functional inactivation of C3b receptors. Degradation of trichloroacetic acid non-precipitable protein of [125I]-AIgG40 by 10(6) macrophages was 38 +/- 6% in medium alone and 60 +/- 8% in the presence of 10% fresh guinea-pig serum (NGPS) after 60 min at 37 degrees. The inactivation of 25%, 50%, 72% and 94% of C3b receptors by trypsin did not affect the degradation of AIgG40 in medium alone, but decreased degradation from 69% to 58%, 47%, 32% and 13% of AIgG40 respectively, in the presence of 10% GPS. Macrophages (10(6)) in medium alone degraded 40%, 47%, 65% and 68% of AIgG40 bearing 0, 5, 10, 16 and 20 C3b molecules per aggregate, indicating a dose-dependent enhancement of degradation by bound C3b; conversely, inactivation of 95% of C3 receptor on the macrophages resulted in 39%, 30%, 12%, 5% and 6% degradation of these AIgG40-C3b, indicating a dose-related inhibition by aggregate-bound C3b in the absence of cellular C3 receptor. These experiments stress the importance of Fc and C3b receptor co-operation and immune complex bound C3b.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002478:Cells, Cultured; D003179:Complement C3b / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011951:Receptors, Complement / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D011951:Receptors, Complement; D011961:Receptors, Fc; D003179:Complement C3b; D014357:Trypsin