ABSTRACT
The proinflammatory activities of the complement system are mostly mediated by the anaphylatoxins, C3a, C4a, and C5a. The isolation of the anaphylatoxins from complement-activated serum, and their production via recombinant technology, has led to a better refinement of their individual functional activities as well as their structural characteristics. The role of C3a in mediating proinflammatory responses is believed to be much more restricted than that of C5a. In addition, C3a is at least tenfold less active in inducing these responses compared to C5a. Multiple alignment of the amino acid sequences of the three anaphylatoxins shows that 15 residues have been totally conserved between C3a, C4a, and C5a, six of which are the immutable disulfide bond forming cysteine residues. The anaphylatoxins are remarkable proteins with respect to their high resistance to denaturation and ability to spontaneously refold to their native structure upon removal of the denaturing conditions.
