title: Innate immune response triggered by triacyl lipid A is dependent on phospholipid transfer protein (PLTP) gene expression.
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. 35+/-7%, 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.
authors.affiliation: Centre de Recherche INSERM UMR866, Université de Bourgogne, Faculté de Médecine, 7 boulevard Jeanne d'Arc, BP87900, 21079 Dijon Cedex, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.forename: Catherine
authors.initials: C
authors.lastname: Paul
authors.forename: Valérie
authors.initials: V
authors.lastname: Deckert
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.forename: Alexis
authors.initials: A
authors.lastname: Klein
authors.forename: Jérôme
authors.initials: J
authors.lastname: Labbé
authors.forename: Naig
authors.initials: N
authors.lastname: Le Guern
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.forename: Serge
authors.initials: S
authors.lastname: Monier
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.forename: Ali
authors.initials: A
authors.lastname: Bettaieb
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jeannin
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008050:Lipid A / Q000276:immunology* / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D008050:Lipid A; D049294:Phospholipid Transfer Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma