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Libert, C.* ; Wielockx, B.* ; Grijalba, B.* ; van Molle, W.* ; Kremmer, E. ; Colten, H.R.* ; Fiers, W.* ; Brouckaert, P.*

The role of complement activation in tumour necrosis factor-induced lethal hepatitis.

Cytokine 11, 617-625 (1999)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Injection of tumour necrosis factor (TNF) in animals causes severe liver cell toxicity, especially when D-(+)-galactosamine (GalN) is co-administered. After challenge with TNF/GalN, serum complement activity (CH50 and APCH50) decreased dramatically, suggesting strong activation of both the classical and the alternative pathways. TNF or GalN alone had no such effect. A cleavage product of complement protein C3 [C3(b)] was deposited on the surface of hepatocytes of TNF/GalN-treated mice. Intravenous administration of cobra venom factor (CVF), which depletes complement, inhibited the development of hepatitis. However, CVF pretreatment also protected C3-deficient mice. Pretreatment of mice with a C1q-depleting antibody did not prevent TNF/GalN lethality, although the anti-C1q antibody had depleted plasma C1q. Factor B-deficient and C3-deficient mice, generated by gene targeting, proved to be as sensitive to TNF/GalN as control mice. Furthermore, induction of lethal shock by platelet-activating factor, an important mediator in TNF-induced hepatic failure, was not reduced in C3-deficient mice. These data indicate that complement, although activated, plays no major role in the generation of acute lethal hepatic failure in this model and that CVF-induced protection is independent of complement depletion.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords complement hepatitis knockout mice shock tumour necrosis factor
ISSN (print) / ISBN 1043-4666
e-ISSN 1096-0023
Journal Cytokine
Quellenangaben Volume: 11, Issue: 8, Pages: 617-625 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Oxford [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)