Evidence for direct renal injury as a consequence of glomerular complement activation.
An isolated perfused kidney (IPK) preparation was used to study the functional consequences of antibody-initiated glomerular complement activation in an environment devoid of circulating inflammatory cells. Control IPK, with antibody bound to the glomerular basement membrane (GBM) (mean +/- SEM, 165.0 +/- 5.7 micrograms globulin/g renal cortex), were perfused with a 5% albumin solution. Control urinary protein excretion was 0.306 +/- 0.112 mg/min, renal vascular resistance (RVR) was 4.72 +/- 0.69 mgHg/ml/min, and the glomerular filtration rate (GFR) was 0.41 +/- 0.01 ml/min/g. To produce glomerular complement activation, IPK with equal quantities of bound antibody (167.0 +/- 6.1 micrograms/g) were perfused with fresh plasma. Glomerular complement activation was associated with linear deposition of C3 on the GBM, a significant increase in protein excretion (3.317 +/- 1.077 mg/min; p less than 0.001) and RVR (10.15 +/- 1.85 mmHg/ml/min; p less than 0.001), and a decline in GFR (0.38 +/- 0.01 ml/min/g; p less than 0.05). Equivalent IPK perfused with decomplemented plasma demonstrated neither glomerular complement deposition nor augmented renal injury. By using both complement repletion and depletion techniques, this study demonstrates that antibody-initiated glomerular complement activation produces direct, neutrophil-independent renal injury. Thus, activated complement components may directly contribute to antibody-induced immune renal injury, in addition to their well established role in the recruitment of circulating inflammatory cells.
D000818:Animals; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010477:Perfusion; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep
D004546:Elapid Venoms; D007074:Immunoglobulin G; C016310:cobra venom factor; D003165:Complement System Proteins