Complement fixation in acute serum sickness: assembly of glomerular-bound C3-convertase.
Complement (C) fixing properties of glomerular immune deposits were studied in vitro in two groups of rabbits with acute serum sickness (ASS). Deposits were studied early in decomplemented (cobra venom factor-treated) rabbits (Group I) and during the evolution of the nephritis in non-decomplemented rabbits (Group II). Following perfusion of kidneys of animals from Group I (which contained no autologous C3) with rabbit serum deficient in factor B (classical pathway) or serum pre-treated with Mg++EGTA (alternative pathway), fixation of C3 was observed in both systems. No C3 deposition was found when EDTA-rabbit serum was used. When kidney sections obtained from serial biopsies and autopsy material from Group II (which contained rabbit C3-C3rb) were incubated with purified factors B and D, followed by either purified human C3 (C3hu) or EDTA-guinea-pig serum (C3gp), fixation of C3hu or C3gp to early C3 deposits was observed. When sections were pre-incubated with heat-inactivated rabbit serum (source of C3b-inactivator), C3 fixation was substantially reduced. Little or no C3 fixation was found after incubation of sections with human or guinea-pig serum depleted of factor D (classical pathway). Thus, in ASS, glomerular complement deposition appears to be predominantly dependent on the activation of the alternative pathway (C3b-feedback) which is progressively lost during the evolution of the nephritis.
D000818:Animals; D000936:Antigen-Antibody Complex; D003166:Complement Activating Enzymes / Q000276:immunology*; D003176:Complement C3 / Q000172:deficiency / Q000276:immunology*; D050577:Complement C3-C5 Convertases / Q000276:immunology*; D003168:Complement Fixation Tests; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology*; D008297:Male; D011817:Rabbits; D012713:Serum Sickness / Q000276:immunology*
D000936:Antigen-Antibody Complex; D003176:Complement C3; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases