Formation of the terminal complement complex on agarose beads: further evidence that vitronectin (complement S-protein) inhibits C9 polymerization.
Vitronectin occupies the metastable binding site of C5b-7, which is unable to insert membranes as part of the complement lytic attack. Some evidence has been presented that vitronectin inhibits also membrane-associated pore formation by inhibiting C9 polymerization in the terminal complement complex (TCC). The authors wished to add to this background by studying the effect of vitronectin on formation of TCC on a carbohydrate surface like agarose beads, an alternative complement pathway activator. Bound TCC was detected by monoclonal and polyclonal antibodies to C9-neoepitopes. Soluble SC5b-7 and TCC (SC5b-9) did not bind to the agarose beads. Using serum or isolated complement factors for the alternative and terminal pathways, the authors found that vitronectin reduced the density of C9-neoepitopes on the beads. As there was no convincing evidence for association of vitronectin with the factors C5b-8 of the agarose-bound TCC, it was concluded that vitronectin bound directly to C9 in TCC and inhibited C9 polymerization within the complex. The authors have shown that TCC can bind to a carbohydrate surface like agarose (an alternating polymer of galactose moieties) in the absence of lipid. These results suggest that vitronectin can limit the lytic effect of membrane-bound TCC by inhibiting C9 polymerization.
Johnson
E
E
Research Forum, Ullevål Hospital, Oslo, Norway.
Berge
V
V
Høgåsen
K
K
D000818:Animals; D003186:Complement C9 / Q000378:metabolism; D011415:Complement Factor B / Q000494:pharmacology; D015938:Complement Membrane Attack Complex / Q000187:drug effects / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008863:Microspheres; D011108:Polymers; D012685:Sepharose; D012995:Solubility; D019096:Vitronectin
D003186:Complement C9; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D011108:Polymers; D019096:Vitronectin; D012685:Sepharose; D011415:Complement Factor B