Glomerular injury and proteinuria in rats after intrarenal injection of cobra venom factor. Evidence for the role of neutrophil-derived oxygen free radicals.
The purpose of these studies was to determine how intravascular complement activation could lead to glomerular injury. Cobra venom factor (CVF) infused into the renal artery of rats resulted in increased excretion of protein in urine, which was maximal over the first 24 hours (51.2 +/- 6.0 mg/24 hours in CVF versus 14.1 +/- 0.9 mg/24 hours in saline-treated animals; P less than 0.001). Depletion of circulating neutrophils with anti-neutrophil serum significantly reduced the CVF-induced proteinuria in the first 24 hours (neutrophil depleted rats 22.7 +/- 2.8 mg/24 hours versus 63.4 +/- 9.9 mg/24 hours in neutrophil intact rats; P less than 0.005). Morphologic abnormalities (which were quantitated morphometrically) included accumulation of neutrophils in glomerular capillary loops, blebbing of endothelial cells, and epithelial cell foot process fusion. The increased protein excretion was reduced by 70% by simultaneous administration of catalase (23 +/- 4.3 mg/24 hours in CVF plus catalase versus 52.1 +/- 10 mg/24 hours in CVF alone; P less than 0.05). Catalase reduced glomerular endothelial cell blebbing and epithelial cell foot process fusion but not neutrophil accumulation in glomeruli as assessed by morphometry. In similar experiments superoxide dismutase, dimethyl sulfoxide, and deferoxamine did not prevent CVF-induced proteinuria. These studies, therefore, suggest that intravascular activation of complement in the rat causes glomerular injury and proteinuria which is dependent on neutrophils and upon the generation of hydrogen peroxide and/or its metabolites.
Rehan
A
A
Wiggins
R C
RC
Kunkel
R G
RG
Till
G O
GO
Johnson
K J
KJ
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004546:Elapid Venoms / Q000037:antagonists & inhibitors / Q000276:immunology*; D005609:Free Radicals; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D011507:Proteinuria / Q000209:etiology* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery; D013194:Staining and Labeling; D013482:Superoxide Dismutase / Q000494:pharmacology
D004546:Elapid Venoms; D005609:Free Radicals; D011506:Proteins; C016310:cobra venom factor; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D010100:Oxygen; D004121:Dimethyl Sulfoxide