Mononuclear phagocytic system stimulation. Protective role from glomerular immune complex deposition.
Experimentally, glomerular deposition of circulating IC is increased when the MPS is saturated. Clinically, an association between glomerulonephritis and dysfunction of MPS-Fc receptor-mediated clearance of IC has recently been described in patients with certain forms of autoimmune diseases. Thus we hypothesized that stimulation of the MPS may be beneficial, by decreasing circulating IC and hence, reduce glomerular deposition of IC. To test this experimentally, we studied glomerular uptake and disappearance of AHIgG . 125I (macromolecular proteins biologically akin to IC) in normal control rats and in rats with ZY-stimulated MPS. ZY-treated and control rats were given 30 mg/100 gm body weight AHIgG . 125I and sacrificed at 30 min and 1, 2, 4, 8, 16, and 24 hr after AHIgG . 125I injection. Glomerular AHIgG . 125I was measured in preparations of isolated glomeruli and compared to simultaneous liver, spleen, lung, and blood greater than 7S AHIgG . 125I. The blood t 1/2 of greater 7S AHIgG . 125I in ZY rats was 40% shorter than that in control rats. Blood greater than 7S AHIgG . 125I in ZY rats was 63% lower than in control rats at 4 hr and 73% lower at 8 hr after injection. At all time intervals, glomerular AHIgG . 125I was reduced in ZY rats proportionately to the decreased blood levels. By immunofluorescence microscopy, the intensity of staining for human IgG correlated with the quantitative determination of AHIgG . 125I in preparations of isolated glomeruli in control and ZY rats. The reduction in blood and glomerular AHIgG . 125I in ZY rats was a result of a marked increased in hepatic and splenic uptake of AHIgG . 125I. Serum complement depletion of ZY rats with CVF prior to AHIgG . 125I injection did not significantly alter the kinetics of AHIgG. 125I. This suggests that the increased MPS uptake of AHIgG . 125I in ZY rats was predominantly Fc-receptor-mediated. Thus ZY stimulation of the MPS increased the clearance of AHIgG . 125I and protected glomeruli from AHIgG . 125I deposition. Clinically, agents that would specifically stimulate the MPS may be useful in reducing IC-mediated glomerular injury.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D007074:Immunoglobulin G / Q000032:analysis; D007457:Iodine Radioisotopes; D007668:Kidney / Q000033:anatomy & histology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000032:analysis; D008297:Male; D010586:Phagocytes / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000032:analysis; D013268:Stimulation, Chemical
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes