Control of the immune complex-complement interaction by protein H of the alternative complement pathway and the natural inhibitor heparin.
The potential of the negative regulatory protein H of the alternative complement pathway convertase and of heparin in modulating the complement-dependent capacity of fresh serum to inhibit immune complex precipitation (CIICP) between bovine serum albumin (BSA) and rabbit anti-BSA as well as tetanus toxoid (TT) and human anti-TT was assessed. Additions of purified H to serum to increase the intrinsic concentration of this protein by 80% (BSA-anti-BSA system) and 190% (TT-anti-TT system) resulted in an inhibition of CIICP by 50% and 60%, respectively, whereas further increase of the amount of H lead to a decrease of its inhibitory activity. A similar effect was observed with heparin: at a concentration of 400 U/ml a 90% inhibition of CIICP in the TT-anti-TT system was obtained which diminished at higher heparin concentrations. The effect of H on C3 deposition to immune aggregates was assessed through its influence on C3b-mediated immune adherence hemagglutination; factor H dose-dependently suppressed such hemagglutination induced by aggregated human IgG or preformed TT-anti-TT complexes when added to the immune complex-fresh serum mixture at the outset but not after 45 min of the 37 degrees C incubation period which means that H inhibited more likely decoration of immune complexes with C3b than it did inhibit the interaction of C3b-coated immune complexes with erythrocytes. This suppressive effect of H was reversed by the simultaneous addition of the activating protein B. Complement-mediated binding of tritiated C3 to latex-bound human IgG was assessed and H was found to dose-dependently inhibit such binding with a maximal inhibition of 37% at a H concentration of 7 micrograms/ml.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D011232:Chemical Precipitation; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000502:physiology*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D006168:Guinea Pigs; D006384:Hemagglutination; D006493:Heparin / Q000502:physiology*; D006801:Humans; D011817:Rabbits; D012397:Rosette Formation; D012710:Serum Albumin, Bovine / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology
D000936:Antigen-Antibody Complex; C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D013745:Tetanus Toxoid; D012710:Serum Albumin, Bovine; D003179:Complement C3b; D017242:Complement Factor H; D006493:Heparin