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.