Human CETP lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice.
Fiche publication
Date publication
décembre 2020
Journal
Journal of lipid research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAGROST Laurent, Dr PAIS DE BARROS Jean-Paul
Tous les auteurs :
Dusuel A, Deckert V, Pais DE Barros JP, Van Dongen K, Choubley H, Charron E, Le Guern N, Labbé J, Mandard S, Grober J, Lagrost L, Gautier T
Lien Pubmed
Résumé
Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.
Mots clés
CETP, Cholesterol, Endotoxins, HDL, Inflammation, Lipid transfer proteins, Lipoproteins, Sepsis, Transgenic mice
Référence
J Lipid Res. 2020 Dec 9;: