Human cholesteryl ester transfer protein lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice - Archive ouverte HAL Access content directly
Journal Articles Journal of Lipid Research Year : 2020

Human cholesteryl ester transfer protein lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice

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Aloïs Dusuel
  • Function : Author
  • PersonId : 1085341
Valérie Deckert
  • Function : Author
  • PersonId : 997685
Naïg Le Guern
  • Function : Author
  • PersonId : 997686
Stéphane Mandard
  • Function : Author
  • PersonId : 872621
Jacques Grober
Laurent Lagrost
  • Function : Author
  • PersonId : 849496
Thomas Gautier
  • Function : Author
  • PersonId : 982822

Abstract

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.
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Dates and versions

inserm-03052637 , version 1 (10-12-2020)

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Aloïs Dusuel, Valérie Deckert, Jean-Paul Pais de Barros, Kevin van Dongen, Hélène Choubley, et al.. Human cholesteryl ester transfer protein lacks lipopolysaccharide transfer activity, but worsens inflammation and sepsis outcomes in mice. Journal of Lipid Research, 2020, pp.jlr.RA120000704. ⟨10.1194/jlr.RA120000704⟩. ⟨inserm-03052637⟩
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