Mediator systems in a passive model of in situ immune complex glomerulonephritis. Role for complement, polymorphonuclear granulocytes and monocytes.
The pathogenetic roles of complement, polymorphonuclear granulocytes, and monocytes were studied in a model of in situ immune complex glomerulonephritis employing a cationized antigen. Left kidneys of Wistar rats were perfused with 40 micrograms of cationized human IgG (isoelectric point greater than or equal to 9.5) followed by intravenous injection of rabbit anti-human IgG 1 hour later. This resulted in prominent subepithelial deposit formation in the perfused kidney accompanied by massive proteinuria. Groups examined were: (a) no additional treatment, (b) C3 depleted (cobra venom factor, (c) granulocyte depleted (specific antiserum), (d) monocyte depleted (specific antiserum), and (e) granulocyte depleted and monocyte depleted. The quantity of radiolabeled cationized antigen deposited in the left kidney was not affected by any of the treatment schedules. Proteinuria was abolished in all mediator depleted groups (b to e) for 5 to 7 days, thereafter rising to levels seen in the nondepleted group (a). This late onset of proteinuria is noteworthy since the deposits are then located subepithelially and may be less accessible to circulating mediators. C3 depletion, despite inhibition of proteinuria, did not prevent the intraglomerular accumulation of granulocytes and monocytes thereby suggesting that attraction and activation of these cells may occur independently. Apparently all three mediators are required for full expression of the lesion, a finding not paralleled in other experimental models of glomerulonephritis. The relevance of very low levels of inflammatory cell infiltration for provoking glomerular injury was clearly demonstrated.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002412:Cations; D003176:Complement C3 / Q000276:immunology*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology* / Q000503:physiopathology; D006098:Granulocytes / Q000276:immunology*; D006651:Histocytochemistry; D007105:Immune Complex Diseases / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008854:Microscopy, Electron; D009000:Monocytes / Q000276:immunology*; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains
D000888:Antibodies, Anti-Idiotypic; D002412:Cations; D003176:Complement C3; D007074:Immunoglobulin G