Relative contributions of chemo-attractant and terminal components of complement to anti-glomerular basement membrane (GBM) glomerulonephritis.
The relative contributions of chemo-attractant and terminal components of complement to heterologous phase glomerular injury was studied in anti-GBM glomerulonephritis in rabbits. Normal rabbits (complement intact) were given anti-GBM antibody at a dose which resulted in 140 micrograms specific kidney-fixed antibody per gram of renal cortex, and developed significant proteinuria (1910 +/- 327 mg/24 h; control 18.2 +/- 6.1 mg/24 h; P less than 0.01). Leucocyte depletion significantly reduced but did not abolish proteinuria (574 +/- 186 mg/24 h, P less than 0.05). Complement depletion of neutrophil-depleted rabbits resulted in a further significant reduction in proteinuria 50.1 +/- 12.2 mg/24 h, P less than 0.05; versus neutrophil-depleted, complement-intact rabbits), indicating that both neutrophil accumulation and complement activation independent of neutrophils contribute to injury in this model. Rabbits congenitally deficient in the sixth component of complement (C6D) developed similar levels of proteinuria (2099 +/- 796 mg/24 h) to normal rabbits given an identical dose of antibody. However, after leucocyte depletion, C6D rabbits developed significantly less proteinuria (135 +/- 56 mg/24 h) than did leucocyte-depleted, complement-intact rabbits (P less than 0.05). These studies show that terminal complement components are not necessary for the full expression of acute anti-GBM antibody-initiated injury in leucocyte-intact rabbits. However, in the absence of leucocytes, C6 and the terminal complement components are apparently responsible for the majority of the complement-dependent glomerular injury.
Tipping
P G
PG
Monash University, Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Boyce
N W
NW
Holdsworth
S R
SR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies; D001485:Basement Membrane / Q000276:immunology; D003176:Complement C3 / Q000032:analysis; D003183:Complement C6 / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D015433:Glomerulonephritis, Membranous / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D011507:Proteinuria / Q000276:immunology; D011817:Rabbits
D000906:Antibodies; D001323:Autoantibodies; D003176:Complement C3; D003183:Complement C6; D015938:Complement Membrane Attack Complex; C051951:antiglomerular basement membrane antibody