Cristin-resultat-ID: 345996
Sist endret: 25. oktober 2016 14:35
Resultat
Vitenskapelig artikkel
2003

Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis

Bidragsytere:
  • Tom Sprong
  • Petter Brandtzaeg
  • Michael Fung
  • Anne Pharo
  • Ernst Arne Høiby
  • Terje Einar Michaelsen
  • mfl.

Tidsskrift

Blood
ISSN 0006-4971
e-ISSN 1528-0020
NVI-nivå 2

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2003
Volum: 102
Sider: 3702 - 3710

Beskrivelse Beskrivelse

Tittel

Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis

Sammendrag

The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effect of complement inhibition on inflammation and bacterial killing. Monoclonal antibodies (mAbs) blocking lectin and alternative pathways inhibited complement activation by N meningitidis and oxidative burst induced in granulocytes and monocytes. Oxidative burst was critically dependent on CD11b/CD18 (CR3) expression but not on Fc gamma-receptors. Specific inhibition of C5a using mAb 137-26 binding the C5a moiety of C5 before cleavage prohibited CR3 up-regulation, phagocytosis, and oxidative burst but had no effect on C5b-9 (TCC) formation, lysis, and bacterial killing. An mAb-blocking cleavage of C5, preventing C5a and TCC formation, showed the same effect on CR3, phagocytosis, and oxidative burst as the anti-C5a mAb but additionally inhibited TCC formation, lysis, and bacterial killing, consistent with a C5b-9-dependent killing mechanism. In conclusion, the anti-C5a mAb 137-26 inhibits the potentially harmful effects of N meningitidis-induced C5a formation while preserving complement-mediated bacterial killing. We suggest that this may be an attractive approach for the treatment of meningococcal sepsis

Bidragsytere

Tom Sprong

  • Tilknyttet:
    Forfatter

Petter Bae Brandtzæg

Bidragsyterens navn vises på dette resultatet som Petter Brandtzaeg
  • Tilknyttet:
    Forfatter

Michael Fung

  • Tilknyttet:
    Forfatter

Anne Pharo

  • Tilknyttet:
    Forfatter

Ernst Arne Høiby

  • Tilknyttet:
    Forfatter
    ved Folkehelseinstituttet
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