Defective function of the mononuclear phagocytic system in rats with chronic nephritis. Evidence of a decreased degradation of IgG aggregates by Kupffer cells.

In a model of chronic nephritis induced by daily injections of ovalbumin (OVA), the fate of stable, well-defined heat-aggregated rat IgG (A-IgG) was examined by comparing it to that observed in normal rats of the same age. Following i.v. injection of traced amounts of 125I-A-IgG 0.5 hr after the administration of OVA (Group I), rats with nephritis showed delayed blood clearance (t1/2 = 4.6 +/- 2.3 min) compared to the control group (t1/2 = 2.4 +/- 0.8 min). At this time, the following data were also obtained from rats with nephritis: (i) sections of liver, examined by immunofluorescence, showed rat IgG in Kupffer cells reflecting the presence of immune complexes (IC), as was demonstrated in blood by the Raji cell assay; and (ii) rosette formation of IgG-sensitized Affigel 701 beads with Kupffer cells demonstrated decreased Fc receptor-ligand binding in comparison to those of control rats (percentage rosettes: 18.3 +/- 7.2 versus 40.9 +/- 7.9; P less than 0.01). To assess the dynamics of the mononuclear phagocytic system (MPS) in the uptake of immune complexes, in another set of experiments the A-IgG was administered 18 hr after the injection of OVA (Group II). Although a delayed blood clearance of A-IgG was also observed (t1/2 = 4.1 +/- 1.2 min) there were neither circulating IgG-immune complexes nor IgG deposits in the liver, and the percentage of rosette-forming Kupffer cells was increased (75.6 +/- 7.4%). To explain the apparently discordant results between the t1/2 and percentages of rosette-forming Kupffer cells in Group II, binding assays (at 4 degrees and 37 degrees), endocytosis, and catabolism of labelled A-IgG for Kupffer cells were studied. The binding studies at 4 degrees showed that the number of receptor sites per cell was similar in rats with nephritis (6.5 +/- 3.3 X 10(4] and control rats (7.0 +/- 3.1 X 10(4]. However, in rats with nephritis, the affinity constant Ka was significantly lower (0.86 +/- 0.4/M X 10(8] than in control rats (37.4 +/- 13.9/M X 10(8); P less than 0.01). The endocytosis rates of rats with nephritis were significantly decreased throughout the whole period of study compared to control rats, while the catabolism was only different during the final period of the study. On the whole, these data suggest that rats with induced chronic nephritis present an impairment in the immune clearance of IgG aggregates, probably due to decreased processing by Kupffer cells.