Activation of the classical complement pathway by nephritic factor bound to the alternative pathway C3/C5 convertase.
Nephritic Factor (NF), the potent alternative pathway activator, which is occasionally found in association with certain types of nephritis has recently been identified as an IgG class autoantibody specific for the C3 convertase (C3bB) of the alternative pathway. In these studies we have examined the possibility that the cell-bound NF-stabilized C3 convertase (EC3 bBNF) binds and activates the first component of the classical pathway of complement. EC3bBNF bound C1q, and the extent of binding was dependent upon the number of NF molecules bound per cell and decreased parallel to the dissociation and release of NF from the cells. Interaction of C1 with bound NF resulted in its activation as shown by the proteolytic conversion of proenzyme C1s to its activated form C1s. As was the case with C1q binding, C1 activation was dependent on the number of NF molecules bound per cell. Thus the NF-stabilized C3 convertase binds and activates C1.
D001665:Binding Sites; D003166:Complement Activating Enzymes; D003167:Complement Activation; D003172:Complement C1; D003178:Complement C3 Nephritic Factor; D050577:Complement C3-C5 Convertases; D003182:Complement C5; D003169:Complement Inactivator Proteins; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D009393:Nephritis / Q000276:immunology
D003172:Complement C1; D003178:Complement C3 Nephritic Factor; D003182:Complement C5; D003169:Complement Inactivator Proteins; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases