Relative resistance of the F-42-stabilized classical pathway C3 convertase to inactivation by C4-binding protein.
The sera of some patients with SLE contain an IgG antibody (F-42) directed against the classical pathway C3 convertase (C-42), which is capable of stabilizing C42 in a dose-dependent manner. The half-life (T 1/2) of C42 is prolonged by F-42. In order to determine whether C4-binding protein was capable of reversing stabilization of C42, stabilized and unstabilized cell-bound C42 were exposed to purified C4-bp and the convertase activity was assessed. C4-bp was capable of accelerating the decay of C42 in a dose-dependent manner; 2 microgram/ml C4-bp reduced the T 1/2 of C42 from 5 to 2.5 min at 30 degrees C. On the other hand, 16 microgram C4-bp could reverse stabilization of C42 by F-42 from T 1/2 = 78 min to a T 1/2 - 40 min; 128 microgram C4-bp reduced the T 1/2 of stabilized C42 to 4 min. Functional inactivation of C42 occurs via enhanced decay-dissociation of C2 from the convertase by C4-bp, as shown by the release of 125I-C2i from the cell-bound convertase. Stabilization of C42 by F-42 is caused by prevention of decay-dissociation of 125I-C2. F-42 was also capable of stabilizing C4oxy2 even further, as shown by prolongation of the T 1/2 of cell-bound C4 oxy2 to a T 1/2 of at least 300 min at 30 degrees C.
D000906:Antibodies; D002352:Carrier Proteins; D003166:Complement Activating Enzymes; D003167:Complement Activation; D003175:Complement C2; D050577:Complement C3-C5 Convertases; D003181:Complement C4; D003171:Complement Pathway, Classical; D004306:Dose-Response Relationship, Immunologic; D006801:Humans
D000906:Antibodies; D002352:Carrier Proteins; D003175:Complement C2; D003181:Complement C4; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases