Complement-independent nephrotoxic nephritis in the guinea pig.
Immunologic mechanisms of proteinuria were investigated in guinea pigs (GP) injected with sheep antiserum (NTS) to GP glomerular basement membrane (GBM). Linear deposition of sheep gamma 1 and gamma 2 IgG led to a prompt but transient (36 hr) increase in albumin excretion from control values of 0.026 +/- 0.013 mg/hr to maximal values of 26+/-12.1 mg/rh at six hours without detectable histologic or electron microscopic changes except for decreased staining for glomerular polyanion and epithelial cell foot process fusion. GBM permeability to anionic ferritin was not increased during proteinuria. Anti-GBM antibody deposits did not fix GP C3 or C4 in vivo or in vitro. NTS-induced proteinuria was the same in guinea pigs that were normal, greater than 95% depleted of C3 through C9, genetically deficient in C4, and depleted of circulating polymorphonuclear leukocytes (PMN). Prior administration of antihistamines, steroids, azathioprine, colchicine, indomethacin, heparin, aprotinin (Trasylol), and niridazole also failed to reduced proteinuria. Initial proteinuria subsided by 36 hr, did not recur despite linear deposition of GP gemma 1 and gemma 2 after day seven, and antibody to GMB-bound sheep globlin. In the GP nephrotoxic nephritis model, anti-GBM antibody deposits apparently mediate increased permeability to albumin by a currently undefined mechanism which is independent of complement, PMN, and other know mediators of inflammation.
D000818:Animals; D000906:Antibodies; D007611:Aprotinin / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D001485:Basement Membrane / Q000473:pathology; D003078:Colchicine / Q000008:administration & dosage; D003165:Complement System Proteins; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D006493:Heparin / Q000008:administration & dosage; D006634:Histamine H1 Antagonists / Q000008:administration & dosage; D006651:Histocytochemistry; D007106:Immune Sera; D007213:Indomethacin / Q000008:administration & dosage; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D009560:Niridazole / Q000008:administration & dosage; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology*; D012756:Sheep / Q000276:immunology
D000906:Antibodies; D006634:Histamine H1 Antagonists; D007106:Immune Sera; D006493:Heparin; D003165:Complement System Proteins; D007611:Aprotinin; D001379:Azathioprine; D009560:Niridazole; D003078:Colchicine; D007213:Indomethacin