ラット慢性血清病腎炎発症後の免疫病理学的検討

The kinetics of immune complexes, the immune deposits and glomerular changes were studied in nephrotic rats. Chronic serum sickness was induced in rats and examined for 80 weeks, injections of bovine serum albumin (BSA) having been stopped at the 13th week. The amount of ciculating immune complexes (CIC) was significantly lower in nephrotic rats than in non-nephrotic rats at the 13th week. To study the short-term kinetics of CIC, 2 mg of BSA was administered intravenously to both groups of rats at the 13th weeek and serum CIC were tested for 24 hrs. Injection of BSA was followed by an acute rise in the titer, which disappeared more rapidly in nephrotic than non-nephrotic rats (12% vs 45% of peak CIC level, 24 hrs after injection). The kinetics of CIC after the injection of 125I·BSA was also studied. The 125I·BSA level, 24 hrs after injection in a nephrotic rat was 8% in blood and 68% in urine. CIC titer seemed to be lowered rapidly due to urinary losses. Histologically, light microscopic changes mainly involved irregularity, thickening and disruption of glomerular basement membrane (GBM). By the 80th week, all changes had resolved apart from persistent GBM thickening. By electron microscopy, subepithelial deposits had been decreased in number after the stoppage of injection of BSA and some of the subepithelial deposits had been completely resolved and some had been covered by a layer of lamina densa-like material and transformed into intramembranous deposits. Deposits had been lucent peripherally and became lucent completely at the 60th week. Subepithelial deposits disappeared after 80 weeks from the GBM. By immunofluorescent staining, BSA decreased in intensity and became negative by the 15th week. Similarly C3 became negative by the 20th week but rat IgG persisted until the 45th week. The presense of lucent deposits correlated with the loss of biological activity as detected by immunofluorescence. Thus the resolution of immune deposits in this model conformed to previously described changes in resolving human membranous nephropathy.