title: Generation of an activated form of human C5 (C5b-like C5) by oxygen radicals.
abstract: Treatment of purified human C5 with hydrogen peroxide leads to a reduction of functional activity in the classical immune haemolysis assay. The effect of H2O2 is enhanced by traces of iron-EDTA, and becomes even stronger when ascorbic acid is present in addition. The enhancement by iron and protective effects of various radical scavengers indicate that the conversion of C5 is brought about by hydroxyl radicals mainly, generated from H2O2 during its decomposition. By the conversion C5 acquires a new functional property: it becomes capable of binding C6, and the resulting complex C56 lyses non-sensitized red cells in cooperation with the late components C7, C8, and C9 (reactive lysis). In this respect, H2O2-treated C5 resembles the activation fragment of C5, C5b. However, unlike C5b, C5(H2O2) is not fragmented but comprises the whole molecule, according to polyacrylamide gel electrophoresis. In accordance with the lack of cleavage, no chemotactic activity indicating formation of C5a, became apparent after H2O2 treatment of C5. In whole human serum, however, the H2O2 system induces additional processes leading to the generation of C5a activity and indicating C5 cleavage. The pathways to this reaction are as yet not clear. The effect of oxygen radicals on C5 may be the basis of the enhancing effect of stimulated leukocytes on C5 activation in body fluids. Activated leukocytes are known to produce H2O2 and oxygen radicals.
mesh_terms: D003167:Complement Activation / Q000187:drug effects*; D003182:Complement C5 / Q000276:immunology* / Q000378:metabolism; D050776:Complement C5b; D003183:Complement C6 / Q000276:immunology; D005609:Free Radicals; D006462:Hemolytic Plaque Technique; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques
chemical_list: D003182:Complement C5; D003183:Complement C6; D005609:Free Radicals; D050776:Complement C5b; D006861:Hydrogen Peroxide