title: Effect of plasma phospholipid transfer protein deficiency on lethal endotoxemia in mice.
abstract: 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 gene family includes the phospholipid transfer protein (PLTP). Here we show that the intravascular redistribution of LPS from the plasma lipoprotein-free fraction toward 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 proinflammatory cytokines were found in PLTP-deficient as compared with wild type mice. Similar inflammatory damage occurred in tissues from wild type and PLTP-deficient mice 24 h after one single intraperitoneal injection of LPS but 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 further supported 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.
authors.affiliation: INSERM, Centre de Recherche-UMR866, Faculté de Médecine, Institut Fédératif de Recherche Santé-STIC, Universitéde Bourgogne, 21079 Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.forename: Alexis
authors.initials: A
authors.lastname: Klein
authors.forename: Valérie
authors.initials: V
authors.lastname: Deckert
authors.forename: Catherine
authors.initials: C
authors.lastname: Desrumaux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ogier
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Sberna
authors.forename: Catherine
authors.initials: C
authors.lastname: Paul
authors.forename: Naig
authors.initials: N
authors.lastname: Le Guern
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.forename: Thomas
authors.initials: T
authors.lastname: Montange
authors.forename: Serge
authors.initials: S
authors.lastname: Monier
authors.forename: Françoise
authors.initials: F
authors.lastname: Piard
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
authors.forename: David
authors.initials: D
authors.lastname: Masson
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D051218:Lymphocyte Antigen 96 / Q000097:blood / Q000235:genetics; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000097:blood* / Q000172:deficiency*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D049294:Phospholipid Transfer Proteins; D000099231:Lipopolysaccharide-Binding Protein; C411728:Ly96 protein, mouse; C510091:phospholipid transfer protein, mouse