Abstract
Gold sodium thiomalate (AuTM) in molar concentrations comparable to those observed in plasma of patients undergoing treatment of rheumatoid arthritis inhibits the interaction of C3b, B, and D̄ to form the amplification C3 convertase (C3b,Bb). The inhibitory action of AuTM is dose related and occurs whether or not P is present to stabilize the C3b,Bb convertase. When the convertase is formed in the absence of D̄ so as to be C3b,B, a higher concentration of AuTM is required for inhibition, suggesting an action not only to prevent the association of B with C3b but also on the presentation of the bimolecular complex as a substrate for D̄. Thiomalate alone was not inhibitory and AuTM had no irreversible effects on cell-bound C3b or fluid phase B, D̄, or P. AuTM did not enhance the decay or inhibit the active site of the preformed C3 convertase generated with cleaved or uncleaved B, with or without P stabilization. AuTM is most active in inhibiting convertase formation on cellular intermediates bearing the lowest number of 125I-C3b per cell and requiring development with the highest B concentration, suggesting the binding site on C3b for B as the locus of AuTM action. This interpretation is compatible with the ability of AuTM to prevent B proteolysis during the fluid phase interaction of C3b, B, and D̄. AuTM is a reversible inhibitor of the formation of C3b,Bb, the amplification C3 convertase of the complement system and thus modulates a critical step in the entire reaction sequence.
