Complement mediated inhibition of immune precipitation and solubilization generate different concentrations of complement anaphylatoxins (C4a, C3a, C5a)

Abstract

Complement prevents the formation of insoluble immune complexes (inhibition of immune precipitation (IIP], and solubilizes preformed immune aggregates (solubilization (SOL]. Since the mechanism of complement activation differs in these two reactions, it is possible that they differ also in the amount of complement fragments released, in particular the anaphylatoxins C3a, C5a and C4a. We measured C4 and C3 consumption, and the formation of complement anaphylatoxins during IIP and SOL using two different immune complex models (BSA, rabbit anti-BSA; tetanus toxoid (TT), human anti-TT). At equal immune complex concentrations in both models, SOL was more efficient than IIP at cleaving C3, and more C3a and C5a was released. Comparing the two reactions, C3a formation was followed by more C5 cleavage (C5a) during SOL. Similarly C4a formation (classical pathway activation) was followed by more C3 cleavage (C3a: classical and alternative pathway activations), during SOL. It is suggested that in vivo SOL of insoluble complexes is rapidly accompanied by a damaging phlogistic reaction, whereas IIP produces less inflammation.

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