Regulation of the alternative pathway of human complement by C1q.
The interaction of C1q with C3b and its effect on C3b activities in the alternative pathway of complement (APC) have been studied. Purified C1q markedly inhibited C3b deposition on and lysis of rabbit erythrocytes by the isolated cytolytic APC. It also blocked formation of the C3 convertase, C3b, Bb as well as binding of Factors B and H to sheep erythrocytes (E) bearing C3b. The direct and specific binding of C1q to C3b was clearly demonstrated using the hemagglutination technique at low ionic strength (0.1 M NaCl). C1q concns of 2 micrograms/ml and higher agglutinated, in a dose-dependent fashion, EC3b but not E, EC3bi or EC3d. Addition of C1r and C1s to C1q and formation of C1 did not affect its capacity to agglutinate EC3b. The C1q-mediated agglutination of EC3b was inhibited by EDTA, MgEGTA, C3b and Factor B but not by native C3 or collagen. Heating C1q (56 degrees C) markedly potentiated its agglutinating activity whereas collagenase-treated C1q lost most of its activity. Taken together, these results suggest that C1q binds through its "heads" and in the presence of calcium ions to a site on C3b that is adjacent to the Factor B and Factor H binding sites. This interaction may down-regulate the activity of the alternative pathway of complement on surfaces which activate both the classical and alternative pathways of complement.
D000818:Animals; D003166:Complement Activating Enzymes / Q000378:metabolism / Q000494:pharmacology*; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism / Q000494:pharmacology*; D015922:Complement C1q; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006801:Humans
C493495:CFH protein, human; D003172:Complement C1; D003180:Complement C3b Inactivator Proteins; D015922:Complement C1q; D003179:Complement C3b; D017242:Complement Factor H; D003166:Complement Activating Enzymes; D011415:Complement Factor B