Intra-Abdominal Lipopolysaccharide Clearance and Inactivation in Peritonitis: Key Roles for Lipoproteins and the Phospholipid Transfer Protein

IntroductionDuring peritonitis, lipopolysaccharides (LPS) cross the peritoneum and pass through the liver before reaching the central compartment. The aim of the present study was to investigate the role of lipoproteins and phospholipid transfer protein (PLTP) in the early stages of LPS detoxification.Material and MethodsPeritonitis was induced by intra-peritoneal injection of LPS in mice. We analyzed peritoneal fluid, portal and central blood. Lipoprotein fractions were obtained by ultracentrifugation and fast protein liquid chromatography. LPS concentration and activity were measured by liquid chromatography coupled with mass spectrometry and limulus amoebocyte lysate. Wild-type mice were compared to mice knocked out for PLTP.ResultsIn mice expressing PLTP, LPS was able to bind to HDL in the peritoneal compartment, and this was maintained in plasma from portal and central blood. A hepatic first-pass effect of HDL-bound LPS was observed in wild-type mice. LPS binding to HDL resulted in an early arrival of inactive LPS in the central blood of wild-type mice.ConclusionPLTP promotes LPS peritoneal clearance and neutralization in a model of peritonitis. This mechanism involves the early binding of LPS to lipoproteins inside the peritoneal cavity, which promotes LPS translocation through the peritoneum and its uptake by the liver.

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Abstract 424: Phospholipid Transfer Protein Deficiency Promotes Inflammatory Factors' Expression via TLR4-TAK1-NFκB Pathway in Macrophage

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.424 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Yang Yu

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Factors ◽

Phospholipid Transfer Protein ◽

Wild Type ◽

Transfer Protein ◽

Phospholipid Transfer ◽

Nfκb Pathway ◽

Nuclear Levels ◽

Deficient Mice ◽

Pro Inflammatory Cytokines

Phospholipid transfer protein (PLTP) plays important roles in macrophage mediated inflammation. In the current study we observed that endogenous PLTP modulated pro-inflammatory pathways in macrophage. With the presence of LPS, peritoneal derived macrophage (PDM) or bone marrow derived macrophage (BMDM) from PLTP deficient mice (PLTP-/-) expressed significantly higher level of pro-inflammatory cytokines compared with PDM or BMDM from wild-type mice (WT), respectively. LPS induced TNFα expression in PLTP-/- BMDM or PLTP knockdown RAW264.7 were suppressed by (5Z)-7-Oxozeaenol, a TAK1 inhibitor, suggesting PLTP deficiency enhanced the expression of pro-inflammatory cytokines via TAK1-NFκB pathway in macrophage. Furthermore, abundance of TLR4 on the membrane was dramatically increased in BMDM from PLTP-/- compared with WT. In addition, inhibition of ABCA1 by chemical inhibitor, glyburide, did not reduce nuclear levels of active STAT3 of BMDM, which indicated that no autocrine PLTP triggered ABCA1-JAK2-STAT3 pathway in this study. In conclusion, PLTP deficiency or low expression may enhance LPS induced pro-inflammatory cytokines expression via TLR4-TAK1-NFκB pathway in macrophage.

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Cigarette smoke extract induces the epithelial-to-mesenchymal transition via the PLTP/TGF-β1/Smad2 pathway in RLE-6TN cells

Toxicology Research ◽

10.1039/c6tx00378h ◽

2017 ◽

Vol 6 (2) ◽

pp. 215-222 ◽

Cited By ~ 1

Author(s):

Hong Chen ◽

Feng-ping Wu ◽

Yong-zhen Yang ◽

Xiu-ying Yu ◽

Lu Zhang ◽

...

Keyword(s):

Cigarette Smoke ◽

Epithelial To Mesenchymal Transition ◽

Cigarette Smoke Extract ◽

Phospholipid Transfer Protein ◽

Mesenchymal Transition ◽

Transfer Protein ◽

Phospholipid Transfer ◽

Tgf Β1

Aim: The role of phospholipid transfer protein (PLTP) in the pathogenesis of the cigarette smoke extract (CSE)-induced epithelial-to-mesenchymal transition (EMT) has not been well described.

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