An evaluation of the role of complement depletion in experimental membranous nephropathy in the rat.
Passive Heymann nephritis (PHN), a model of experimental membranous nephropathy produced by the administration of anti-Fx1A antibody, was studied by micropuncture measurement of glomerular hemodynamics and by assessment of immunologic and morphologic findings. The effect of complement depletion on these parameters was evaluated by administering cobra venom factor. Five days after administration of anti-Fx1A Ab to PHN controls, abnormal proteinuria developed and nephron filtration rate decreased due to modest reductions in nephron plasma flow and major reductions (75%) in the glomerular ultrafiltration coefficient. Glomerular capillary hydrostatic pressure gradient was significantly increased and decreased tubular reabsorption was also evident. Complement depletion prevented abnormal proteinuria and normalized tubular reabsorption and some of the glomerular hemodynamic parameters (nephron plasma flow and glomerular capillary hydrostatic pressure gradient). Values for the glomerular ultrafiltration coefficient, a possible index of membrane damage, were significantly improved (100%) after cobra venom factor treatment, although they remained below normal values. Only minimal differences in glomerular and epithelial cell morphology and appearance of electron-dense material were noted between PHN and PHN + cobra venom factor. These data suggest therefore that both complement-dependent and independent mechanisms contribute to explain the changes in nephron filtration and reabsorption that occur in this model of experimental membranous nephropathy.
Gabbai
F B
FB
Veterans Administration Medical Center, San Diego, California.
Mundy
C A
CA
Wilson
C B
CB
Blantz
R C
RC
D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D003165:Complement System Proteins / Q000187:drug effects / Q000502:physiology*; D004546:Elapid Venoms; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D003176:Complement C3; D004546:Elapid Venoms; D026541:Heymann Nephritis Antigenic Complex; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C016310:cobra venom factor; D003165:Complement System Proteins