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

Frej, Cecilia LU ; Linder, Adam LU ; Happonen, Kaisa E. LU ; Taylor, Fletcher B.; Lupu, Florea and Dahlbäck, Björn LU (2016) In Journal of Cellular and Molecular Medicine 20(6). p.1170-1181
Abstract

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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SIRS, Apolipoproteins, HDL, Lipoproteins, Lysophospholipids
in
Journal of Cellular and Molecular Medicine
volume
20
issue
6
pages
12 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:84961262369
ISSN
1582-1838
DOI
10.1111/jcmm.12831
language
English
LU publication?
yes
id
786ed7bb-d426-4987-954f-570df354ae8c
date added to LUP
2016-07-18 14:40:27
date last changed
2016-11-27 04:41:50
@misc{786ed7bb-d426-4987-954f-570df354ae8c,
  abstract     = {<p>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.</p>},
  author       = {Frej, Cecilia and Linder, Adam and Happonen, Kaisa E. and Taylor, Fletcher B. and Lupu, Florea and Dahlbäck, Björn},
  issn         = {1582-1838},
  keyword      = {SIRS,Apolipoproteins,HDL,Lipoproteins,Lysophospholipids},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1170--1181},
  publisher    = {ARRAY(0xc9a8270)},
  series       = {Journal of Cellular and Molecular Medicine},
  title        = {Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons},
  url          = {http://dx.doi.org/10.1111/jcmm.12831},
  volume       = {20},
  year         = {2016},
}