Evaluation of aggregated IgG in mice as an Fc receptor specific probe of the hepatic mononuclear phagocyte system.
In experimental models of immune complex diseases the hepatic mononuclear phagocyte system removes circulating immune complexes (CIC) by interaction with Fc receptors, and the spleen has a relatively insignificant role in this function. We have used heat-aggregated human IgG (AHGG) to detect altered hepatic mononuclear phagocyte system activity in an acute immune complex model in mice in order to evaluate its suitability for possible use in humans. Immune complexes inhibited the clearance of AHGG, as a function of the dose and of the time after injection of complexes. The delayed clearance resulted from decreased hepatic uptake of the AHGG. Alterations in the comparatively small splenic uptake of AHGG did not correlate with changes in the clearance or the hepatic uptake that were produced by the complexes. Studies with Rose Bengal showed that the complexes caused a small but definite decrease in hepatic blood flow. Immune complexes also inhibited the clearance and hepatic uptake of aggregated mouse albumin and aggregated ovalbumin. The aggregated albumins, however, were cleared very rapidly, indicating high extraction ratios, so their clearance was more affected by the decreased blood flow than the clearance of AHGG. We conclude that a small dose of AHGG is a sensitive probe for hepatic Fc receptor function and has potential for human use.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006207:Half-Life; D006358:Hot Temperature; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology*; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D011961:Receptors, Fc