Plasma PLTP (phospholipid-transfer protein): an emerging role in ‘reverse lipopolysaccharide transport’ and innate immunity

Gautier, Thomas; Lagrost, Laurent

doi:10.1042/bst0390984

Cited by 57 publications

(72 citation statements)

References 56 publications

(46 reference statements)

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“…Finally, calculation of the LAL (activity) to HPLC/MS/MS (mass) LPS ratio is proposed as a relevant method to assess in vivo the effi cacy of the initial step of LPS neutralization [known as the endotoxin-lipoprotein hypothesis ( 29 )]. This step is followed by lipoprotein-mediated transport to the liver and ultimate detoxifi cation in the bile ( 30,31 ).…”

Section: Discussionmentioning

confidence: 99%

Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay

Barros

Gautier

Sali

et al. 2015

Journal of Lipid Research

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106

103

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Systemic infl ammatory response syndrome (SIRS) is defi ned by a cluster of clinical signs that include tachycardia, leukocytosis, tachypnoea, and pyrexia ( 1 ). Although SIRS is a major consequence of sepsis (i.e., a deleterious, nonresolving infl ammatory response to infection that can lead to multiple organ dysfunction and septic shock), it can be caused by many pathological events that are not associated with the bacterial infection ( 1 ). It is of major importance to distinguish between noninfectious SIRS, sepsis, and septic shock in critically ill patients because these groups of patients are markedly different in terms of care and clinical outcome. Positive microbiological identifi cation tests [using conventional microbiological tests or bacterial DNA detection ( 2 ) as well as a number of infl ammatory and infectious biomarkers, including cytokines, procalcitonin, immune cell markers or a combination of these ( 3 )] have been proposed, but at this stage, none has proved to be reliable enough to ascertain the occurrence and extent of infection in high-risk patients with SIRS. Interestingly, and as documented further by our group in the prospective multicenter cohort EPISS study ( 4 ), Gramnegative bacilli are the most frequently identifi ed pathogens in patients with septic shock. In this context, the direct quantitation of the culprit component of the Gram-negative bacterium [i.e., lipopolysaccharide (LPS), which triggers SIRS by interacting with the CD14/Toll-like receptor 4 /myeloid differentiation factor 2 receptor complex at the surface of leukocytes ( 1 ) Abbreviations: 3HM, 3-hydroxymyristic acid or 3-hydroxymyristate; LAL, limulus amebocyte lysate; LOD, limit of detection; LOQ, limit of quantifi cation; LPS, lipopolysaccharide; PLTP, phospholipid transfer protein; SIRS, systemic infl ammatory response syndrome; SOFA, sequential organ failure assessment .

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Section: Discussionmentioning

confidence: 99%

Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay

Barros

Gautier

Sali

et al. 2015

Journal of Lipid Research

Self Cite

106

103

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“…Alternatively, pathogen lipids can be sequestered and cleared from the circulation, potentially diminishing their inflammatory effect (4-6) (Figure 1). In this review we address the hypothesis that sequestration and clearance of pathogen lipids may be beneficial and feasible in treating septic patients (4).…”

Section: Introductionmentioning

confidence: 99%

The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance

Walley

Opal

Stein

et al. 2015

Am J Respir Crit Care Med

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Microbial cell walls contain pathogenic lipids, including LPS in gram-negative bacteria, lipoteichoic acid in gram-positive bacteria, and phospholipomannan in fungi. These pathogen lipids are major ligands for innate immune receptors and figure prominently in triggering the septic inflammatory response. Alternatively, pathogen lipids can be cleared and inactivated, thus limiting the inflammatory response. Accordingly, biological mechanisms for sequestering and clearing pathogen lipids from the circulation have evolved. Pathogen lipids released into the circulation are initially bound by transfer proteins, notably LPS binding protein and phospholipid transfer protein, and incorporated into high-density lipoprotein particles. Next, LPS binding protein, phospholipid transfer protein, and other transfer proteins transfer these lipids to ApoB-containing lipoproteins, including low-density (LDL) and very-low-density lipoproteins and chylomicrons. Pathogen lipids within these lipoproteins and their remnants are then cleared from the circulation by the liver. Hepatic clearance involves the LDL receptor (LDLR) and possibly other receptors. Once absorbed by the liver, these lipids are then excreted in the bile. Recent evidence suggests pathogen lipid clearance can be modulated. Importantly, reduced proprotein convertase subtilisin/kexin type 9 activity increases recycling of the LDLR and thereby increases LDLR on the surface of hepatocytes, which increases clearance by the liver of pathogen lipids transported in LDL. Increased pathogen lipid clearance, which can be achieved by inhibiting proprotein convertase subtilisin/kexin type 9, may decrease the systemic inflammatory response to sepsis and improve clinical outcomes.

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“…40 It was recently shown that there is an alternative route of LPS elimination, by binding to HDL and elimination in the liver. 41 According to Hailman et al, PLTP may be a key mediator in binding LPS to HDL. 42 Incubation of LPS with HDL in the presence of PLTP leads to the binding of the particles.…”

Section: Animal Modelsmentioning

confidence: 99%

“…According to Gautier and Lagrost, PLTP may play a role in the reverse transport of LPS, as in the transport of cholesterol. 41 Mice with naturally high levels of PLTP were observed to have lower concentration of LPS and they develop less severe inflammation. Moreover, the reverse LPS transport via HDL and PLTP may increase the rate of elimination of LPS by biliary excretion.…”

Section: Animal Modelsmentioning

confidence: 99%

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Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis

Chowaniec

Skoczyńska

2018

Adv Clin Exp Med

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Cardiovascular diseases are still the main cause of death in Poland and throughout the world. Independent risk factors of cardiovascular disease, in addition to elevated LDL cholesterol, are both low HDL levels and high levels of non-HDL cholesterol. Plasma phospholipid-transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) both play a major role in the metabolism of those lipoproteins. A lack of these proteins increases HDL and lowers LDL levels. In the light of current knowledge, it seems reasonable to search for compounds that may decrease the activity of CETP, and thus reduce the incidence of cardiovascular disease. Whereas on the one hand there are reports about the adverse effect of torcetrapib and the lack of therapeutic effects of dalcetrapib, on the other hand the question arises whether the CETP inhibitors that are currently in clinical trials will rise to the challenges before them. Currently, it is known that the activity of PLTP, while affecting the metabolism of lipoproteins, especially HDL, plays a major role in atherogenesis. Still, there are some contradictions and controversies about the effect of PLTP on reverse cholesterol transport (RCT). There are a number of studies about the role that PLTP plays in the pathogenesis of various diseases. Further studies are needed to clearly determine the impact of PLTP activity on the formation and development of pathological processes in the cardiovascular system.

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Plasma PLTP (phospholipid-transfer protein): an emerging role in ‘reverse lipopolysaccharide transport’ and innate immunity

Cited by 57 publications

References 56 publications

Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay

Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay

The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance

Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis

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