Effect of plasma phospholipid transfer protein deficiency on lethal endotoxemia in mice. - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2008

Effect of plasma phospholipid transfer protein deficiency on lethal endotoxemia in mice.

Résumé

Lipopolysaccharides (LPS) are components of Gram-negative bacteria. The cellular response from the host to LPS is mediated through stepwise interactions involving the lipopolysaccharide binding protein (LBP), CD14, and MD-2 which produces the rearrangement of TLR4. In addition to LBP, the lipid transfer/lipopolysaccharide binding protein (LT/LBP) gene family includes the phospholipid transfer protein (PLTP). Here we show that the intravascular redistribution of LPS from the plasma lipoprotein-free fraction towards circulating lipoproteins is delayed in PLTP-deficient mice. In agreement with earlier in vitro studies which predicted the neutralization of the endotoxic properties of LPS when associated with lipoproteins, significant increases in the plasma concentration of pro-inflammatory cytokines were found in PLTP-deficient as compared to wild-type mice. Similar inflammatory damage occurred in tissues from wild-type and PLTP-deficient mice 24 hours after one single intraperitoneal injection of LPS, however with a more severe accumulation of red blood cells in glomeruli of LPS-injected PLTP-deficient mice. Complementary ex vivo experiments on isolated splenocytes from wild-type and PLTP-deficient mice came in further support of the ability of cell-derived PLTP to prevent LPS-mediated inflammation and cytotoxicity when combined with lipoprotein acceptors. Finally, PLTP deficiency in mice led to a significant increase in LPS-induced mortality. It is concluded that increasing circulating levels of PLTP may constitute a new and promising strategy in preventing endotoxic shock.

Dates et versions

hal-00284576 , version 1 (03-06-2008)

Identifiants

Citer

Thomas Gautier, Alexis Klein, Valérie Deckert, Catherine Desrumaux, Nicolas Ogier, et al.. Effect of plasma phospholipid transfer protein deficiency on lethal endotoxemia in mice.. Journal of Biological Chemistry, 2008, epub ahead of print. ⟨10.1074/jbc.M802802200⟩. ⟨hal-00284576⟩
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