title: Complement activation induced by purified Neisseria meningitidis lipopolysaccharide (LPS), outer membrane vesicles, whole bacteria, and an LPS-free mutant.
abstract: Complement activation is closely associated with plasma endotoxin levels in patients with meningococcal infections. This study assessed complement activation induced by purified Neisseria meningitidis lipopolysaccharide (Nm-LPS), native outer membrane vesicles (nOMVs), LPS-depleted outer membrane vesicles (dOMVs), wild-type meningococci, and an LPS-free mutant (lpxA(-)) from the same strain (44/76) in whole blood anticoagulated with the recombinant hirudin analogue. Complement activation products (C1rs-C1 inhibitor complexes, C4d, C3bBbP, and terminal SC5b-9 complex) were measured by double-antibody EIAs. Nm-LPS was a weak complement activator. Complement activation increased with preparations containing nOMVs, dOMVs, and wild-type bacteria at constant LPS concentrations. With the same protein concentration, complement activation induced by nOMVs, dOMVs, and the LPS-free mutant was equal. The massive complement activation observed in patients with fulminant meningococcal septicemia is, presumably, an indirect effect of the massive endotoxemia. Outer membrane proteins may be more potent complement activators than meningococcal LPSs.
authors.affiliation: Department of Pediatrics, Ullevål University Hospital, 0407 Oslo, Norway. a.k.bjerre@ioks.uio.no
authors.forename: Anna
authors.initials: A
authors.lastname: Bjerre
authors.forename: Berit
authors.initials: B
authors.lastname: Brusletto
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Fritzsønn
authors.forename: Einar
authors.initials: E
authors.lastname: Rosenqvist
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wedege
authors.forename: Ellen
authors.initials: E
authors.lastname: Namork
authors.forename: Peter
authors.initials: P
authors.lastname: Kierulf
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzaeg
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000633:toxicity*; D003167:Complement Activation / Q000187:drug effects*; D004926:Escherichia coli / Q000472:pathogenicity; D006801:Humans; D008070:Lipopolysaccharides / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D008854:Microscopy, Electron; D009154:Mutation; D009345:Neisseria meningitidis / Q000472:pathogenicity*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008070:Lipopolysaccharides