Non-enzymic activation of the fifth component of human complement, by oxygen radicals. Some properties of the activation product, C5b-like C5.
Purified human C5 was converted non-enzymically to an activated form as defined by its ability to participate in reactive lysis. This conversion occurred following exposure to systems that generate oxygen radicals, namely addition of H2O2 in the presence of ascorbic acid and iron or the addition of xanthine oxidase, acetaldehyde and iron. The conversion of C5 to a functionally active species was iron-dependent and inhibited by hydroxyl radical scavengers such as DMSO. The findings suggest that OH. is the active oxygen species that converts C5. The conversion product of C5, termed C5(H2O2), is C5b-like due to its ability to bind C6 and cause reactive lysis. C5(H2O2) is much more stable than C5b obtained by complement convertases. Although C5(H2O2) has lost the binding site of native C5 for C3b it can be cleaved by complement-derived convertases; the cleavage is, however, less efficient than in the case of native C5. The resulting cleavage product, which is C5a-like, is chemotactic although C5(H2O2) is not chemotactic. C5(H2O2) serves as a better substrate for plasma kallikrein than native C5, resulting in the generation of a C5a-like chemotactic product. These data indicate that oxygen radicals can bring about a conformational change in C5, causing it to behave as a functionally activated molecule of the complement system. This may have implications for the role of complement and its activation in the inflammatory response.
Vogt
W
W
Max Planck Institute for Experimental Medicine, Göttingen, F.R.G.
Damerau
B
B
von Zabern
I
I
Nolte
R
R
Brunahl
D
D
D003167:Complement Activation / Q000187:drug effects*; D003182:Complement C5 / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D015936:Complement C5a / Q000096:biosynthesis; D050776:Complement C5b; D003183:Complement C6 / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides / Q000494:pharmacology*; D017665:Hydroxyl Radical; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D014969:Xanthine Oxidase / Q000494:pharmacology
D003182:Complement C5; D003183:Complement C6; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D015936:Complement C5a; D050776:Complement C5b; D007501:Iron; D014969:Xanthine Oxidase