Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage

Michels, Meta; Japtok, Lukasz; Alisjahbana, Bachti; Wisaksana, Rudi; Sumardi, Uun; Puspita, Mita; Kleuser, Burkhard; Mast, Quirijn de; Ven, A.J.A.M. van der

doi:10.1016/j.jinf.2015.06.014

Cited by 17 publications

(22 citation statements)

References 41 publications

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“…However, in the baboon model erythrocytes decreased later than S1P and we observed no correlation between erythrocyte numbers and S1P. Instead platelet levels followed closely the pattern of S1P and S1P correlated very well with platelets in both human and baboon sepsis, which agrees well with recent observations made in dengue fever [28]. Thrombocytopenia is common in sepsis and is an independent predictor of mortality [45].…”

Section: Discussionsupporting

confidence: 90%

“…In the baboon sepsis model, the decrease in plasma S1P was observed at earlier timepoints than the decrease in apoM, indicating that the S1P-apoM interaction is dynamic and the molecules have distinct clearance pathways. These results also suggest that it is not the decrease in apoM per se that induces a decrease in plasma S1P as has been suggested by others [28,33]. The reduced S1P levels we observed could be because of increased degradation/consumption or decreased synthesis/secretion from S1P-producing cells, for example platelets, erythrocytes and endothelial cells.…”

Section: Discussionsupporting

confidence: 84%

“…The barrier function is enhanced by an induction of cadherin‐containing adherent junctions between endothelial cells following S1P 1 ‐stimulation by S1P . In patients with dengue fever, a disease associated with endothelial hyperpermeability, S1P levels were decreased in patients with plasma leakage compared to patients with no plasma leakage . In addition, S1P‐deficient mice have increased vascular leakage and mortality after anaphylaxis compared to control mice and rats have reduced loss of plasma volume during sepsis after administration of the S1P‐analogue FTY720 , indicating a role for S1P‐regulated events in the pathology of plasma leakage.…”

Section: Introductionmentioning

confidence: 99%

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Sphingosine 1‐phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons

Frej

Linder

Happonen

et al. 2016

J Cellular Molecular Medi

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Sphingosine 1‐phosphate (S1P) is an important regulator of vascular integrity and immune cell migration, carried in plasma by high‐density lipoprotein (HDL)‐associated apolipoprotein M (apoM) and by albumin. In sepsis, the protein and lipid composition of HDL changes dramatically. The aim of this study was to evaluate changes in S1P and its carrier protein apoM during sepsis. For this purpose, plasma samples from both human sepsis patients and from an experimental Escherichia coli sepsis model in baboons were used. In the human sepsis cohort, previously studied for apoM, plasma demonstrated disease‐severity correlated decreased S1P levels, the profile mimicking that of plasma apoM. In the baboons, a similar disease‐severity dependent decrease in plasma levels of S1P and apoM was observed. In the lethal E. coli baboon sepsis, S1P decreased already within 6–8 hrs, whereas the apoM decrease was seen later at 12–24 hrs. Gel filtration chromatography of plasma from severe human or baboon sepsis on Superose 6 demonstrated an almost complete loss of S1P and apoM in the HDL fractions. S1P plasma concentrations correlated with the platelet count but not with erythrocytes or white blood cells. The liver mRNA levels of apoM and apoA1 decreased strongly upon sepsis induction and after 12 hr both were almost completely lost. In conclusion, during septic challenge, the plasma levels of S1P drop to very low levels. Moreover, the liver synthesis of apoM decreases severely and the plasma levels of apoM are reduced. Possibly, the decrease in S1P contributes to the decreased endothelial barrier function observed in sepsis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Sphingosine 1‐phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons

Frej

Linder

Happonen

et al. 2016

J Cellular Molecular Medi

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“…In diabetes, apoM increased in streptozotocin‐induced diabetic mice (Nojiri et al, )and apoM induced insulin secretion (Kurano et al, ). In infectious diseases, decreased apoM is associated with plasma leakage and systemic inflammatory responses (Kumaraswamy et al, ; Michels et al, ). Moreover, because recent elegant studies have demonstrated that apoM‐bound S1P acts exclusively on the S1P 1 receptor (Blaho et al, ; Galvani et al, ), resveratrol could exert several beneficial effects in many other diseases in which this S1P receptor is involved.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol exerts a biphasic effect on apolipoprotein M

Kurano

Hara

Nojiri

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEResveratrol exerts a range of beneficial actions in several areas of pathophysiology, including vascular biology. Here, we have investigated the effects of resveratrol on apolipoprotein M (apoM), a carrier and modulator of sphingosine 1-phosphate (S1P), a vasoactive lipid mediator. EXPERIMENTAL APPROACHWe used a hepatoma cell line (HepG2), human primary hepatocytes and C57BL/6 mice. We measured apoM, S1P and related enzymes, LDL receptors and sirtuin1 activity, using Western blotting, RT-PCR and enzyme assays. We also used si-RNA to knockdown sirtuin1 in HepG2 cells. KEY RESULTSIn cultures of HepG2 cells, resveratrol (1-10 μM) increased intracellular apoM and S1P. High concentrations of resveratrol (100 μM) decreased extracellular (in the culture medium) apoM, whereas moderate concentrations of resveratrol (1-10 μM) increased extracellular apoM. High concentrations of resveratrol also increased LDL receptor expression, while all concentrations of resveratrol activated the histone deacetylase sirtuin1. In cultures of human primary hepatocytes, resveratrol, at all concentrations, increased both intra-and extracellular apoM. When wild-type mice were fed a resveratrol-containing chow (0.3% w/w) for 2 weeks, both the plasma and hepatic apoM and S1P levels were increased. However, the resveratrol diet did not affect hepatic LDL receptor levels in this in vivo study. CONCLUSIONS AND IMPLICATIONSResveratrol increased intra-and extracellular levels of apoM, along with intracellular S1P levels, while a high concentration of resveratrol reduced extracellular apoM. The present findings suggest that resveratrol has novel effects on the metabolic kinetics of S1P, a multi-functional bioactive phospholipid. Abbreviations

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“…However, in many such studies, S1P levels were not directly measured. Similarly, it was shown that levels of S1P and apoM inversely correlated with vascular leakage in humans infected with dengue (Michels et al 2015). Moreover, the ability of ApoM/HDL to act as a biased agonist on S1PR1 inhibits vascular inflammation, which may be related to the cardiovascular protective functions of HDL (Galvani et al 2015).…”

Section: Hepatic Production Of Apom Regulates S1p Plasma Levelsmentioning

confidence: 89%

Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology

Rohrbach

Maceyka

Spiegel

2017

Critical Reviews in Biochemistry and Molecular Biology

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Over 20 years ago, sphingosine-1-phosphate (S1P) was discovered to be a bioactive signaling molecule. Subsequent studies later identified two related kinases, sphingosine kinase 1 and 2, which are responsible for the phosphorylation of sphingosine to S1P. Many stimuli increase sphingosine kinase activity and S1P production and secretion. Outside the cell, S1P can bind to and activate five S1P-specific G protein-coupled receptors (S1PR1–5) to regulate many important cellular and physiological processes in an autocrine or paracrine manner. S1P is found in high concentrations in the blood where it functions to control vascular integrity and trafficking of lymphocytes. Obesity increases blood S1P levels in humans and mice. With the world wide increase in obesity linked to consumption of high-fat, high-sugar diets, S1P is emerging as an accomplice in liver pathobiology, including acute liver failure, metabolic syndrome, control of blood lipid and glucose homeostasis, nonalcoholic fatty liver disease, and liver fibrosis. Here, we review recent research on the importance of sphingosine kinases, S1P, and S1PRs in liver pathobiology, with a focus on exciting insights for new therapeutic modalities that target S1P signaling axes for a variety of liver diseases.

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Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage

Cited by 17 publications

References 41 publications

Sphingosine 1‐phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons

Sphingosine 1‐phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons

Resveratrol exerts a biphasic effect on apolipoprotein M

Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology

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