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- Title
Innate immune response triggered by triacyl lipid A is dependent on phospholipid transfer protein (PLTP) gene expression.
- Authors
Gautier, Thomas; Paul, Catherine; Deckert, Valérie; Desrumaux, Catherine; Klein, Alexis; Labbé, Jérôme; Guern, Naig Le; Athias, Anne; Monier, Serge; Hammann, Arlette; Bettaieb, Ali; Jeannin, Jean-François; Lagrost, Laurent
- Abstract
Hexaacyl lipopolysaccharide (LPS) aggregates in aqueous media, but its partially deacylated lipid A moiety forms monomers with weaker toxicity. Because plasma phospholipid transfer protein (PLTP) transfers hexaacyl LPS, its impact on metabolism and biological activity of triacyl lipid A in mice was addressed. Triacyl lipid A bound readily to plasma high-density lipoproteins (HDLs) when active PLTP was expressed [HDL-associated lipid A after 4.5 h: 59.1±16.0% of total in wild-type (WT) vs. 32.5±10.3% in PLTP-deficient mice, P<0.05]. In the opposite to hexaacyl LPS, plasma residence time of lipid A was extended by PLTP, and proinflammatory cytokines/were produced in higher amounts in WT than PLTP mice (remaining lipid A after 8 h: 53±12 vs. 357%, and IL6 concentration after 4.5 h: 45.5±5.9 vs. 14.6±7.8 ng/ml, respectively; P<0.05 in all cases). After 1 wk, onset of B16-induced melanoma was observed in only 30% of lipid A-treated WT mice, whereas >80% of the untreated WT, untreated PLTP-deficient, or lipid A-treated PLTP-deficient animals bore tumors (P<0.05 in all cases). It is concluded that PLTP is essential in mediating the association of triacyl lipid A with lipoproteins, leading to extension of its residence time and to magnification of its proinflammatory and anticancer properties.
- Subjects
MONOMERS; INFLAMMATION; LIPOPROTEINS; HIGH density lipoproteins; CYTOKINES; CANCER; PHOSPHOLIPIDS; IMMUNE response
- Publication
FASEB Journal, 2010, Vol 24, Issue 9, p3544
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.09-152876