The glomerular mesangium. 3. Acute immune mesangial injury: a new model of glomerulonephritis.
A mechanism of immune glomerular injury is described based on the fixation of antibody (Ab) to an antigen (Ag) that has localized in the glomerular mesangium. Rabbits were given, intravenously (i.v.), aggregated human IgG (AHIgG) or albumin (AHSA) and 10 h later, when the Ag by immunofluorescent microscopy was present in the mesangium, a kidney was removed and transplanted into a normal rabbit. The recipient then received, i.v., rabbit anti-HIgG or anti-HSA. Within minutes of Ab infusion, glomeruli of the donor kidney had polymorphonuclear (PMN) infiltration that over the next few hours became marked and was associated with glomerular cell swelling. At 24 h a decrease in PMN's and early mesangial proliferation was seen. By 3 days there was marked mesangial hypercellularity and increased mesangial matrix. Within minutes after Ab administration rabbit IgG, C3, and fibrin were seen in the glomerular mesangium. There was a fall in complement titer by 1 min after Ab infusion that was due to complement consumption by the donor kidney. Complement then returned to normal levels by 48 h. Significant glomerular injury did not occur (a) in the recipient's own kidney, (b) from Ag administration and transplantation without recipient Ab administration, or (c) from transplantation and Ab administration without prior Ag administration. These studies demonstrated that Ag localized in the glomerular mesangium can react with circulating Ab and complement resulting in severe glomerular injury.
D000818:Animals; D000936:Antigen-Antibody Complex; D000937:Antigen-Antibody Reactions; D001706:Biopsy; D003165:Complement System Proteins / Q000032:analysis; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006041:Goats / Q000276:immunology; D006168:Guinea Pigs / Q000276:immunology; D006801:Humans; D007106:Immune Sera; D007074:Immunoglobulin G / Q000008:administration & dosage; D007275:Injections, Intravenous; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation; D008854:Microscopy, Electron; D011414:Properdin; D011817:Rabbits / Q000276:immunology; D012709:Serum Albumin / Q000008:administration & dosage; D014184:Transplantation, Homologous
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D007074:Immunoglobulin G; D012709:Serum Albumin; D011414:Properdin; D003165:Complement System Proteins