Suppression of antibody synthesis by prostaglandin E as a mechanism for preventing murine immune complex glomerulonephritis.
A model of immune complex glomerulonephritis induced in mice by the daily injection of 4 mg. of apoferritin was used to examine the effect of administration of two prostaglandins, PGE1 and PGE2. The twice daily administration of either PGE1 or PGE2 in pharmacologic doses resulted in significantly less glomerular damage and a shift in the primary location of immune complex deposition from the capillary loops to the mesangium, as demonstrated by immunofluorescence and electron microscopy. The beneficial effect of the prostaglandins was associated with a significant decrease in antiapoferritin antibody levels. A separate study was performed to determine whether the mechanism of decreased antibody levels produced by PGE administration was related to a decrease in the number of plaque-forming cells (PFC). Mice received injections of saline, apoferritin, or apoferritin plus PGE2 for 9 days, and spleen cells were used to determine the number of direct and indirect PFC. No direct PFC were detected in any of the groups. There was no difference in the number of indirect PFC between mice receiving apoferritin and those receiving apoferritin plus PGE2 (98 +/- 13 versus 108 +/- 30), whereas mice receiving saline had no indirect PFC. The prevention of glomerular damage in immune complex glomerulomephritis and the shift in the site of complex deposition induced by PGE1 and PGE2 appear to be caused by reduction in specific antibody synthesis. This reduced synthesis is not related to an alteration in the number of antibody-producing cells.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000936:Antigen-Antibody Complex / Q000276:immunology; D001052:Apoferritins / Q000276:immunology / Q000494:pharmacology; D004347:Drug Interactions; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology*; D007105:Immune Complex Diseases / Q000139:chemically induced / Q000276:immunology*; D007074:Immunoglobulin G; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D011458:Prostaglandins E / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D011458:Prostaglandins E; D001052:Apoferritins