title: Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage.
abstract: BACKGROUND
  A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the decrease in S1P levels in dengue.
  
  
  METHODS
  We determined circulating levels of S1P in 44 Indonesian adults with acute dengue and related levels to plasma leakage, as determined by daily ultrasonography, and to levels of its chaperone apolipoprotein M, other lipoproteins and platelets.
  
  
  RESULTS
  Plasma S1P levels were decreased during dengue and patients with plasma leakage had lower median levels compared to those without (638 vs. 745 nM; p < 0.01). ApoM and other lipoprotein levels were also decreased during dengue, but did not correlate to S1P levels. Platelet counts correlated positively with S1P levels, but S1P levels were not higher in frozen-thawed platelet rich plasma, arguing against platelets as an important cellular source of S1P in dengue.
  
  
  CONCLUSIONS
  Decreased plasma S1P levels during dengue are associated with plasma leakage. We speculate that decreased levels of ApoM underlies the lower S1P levels. Modulation of S1P levels and its receptors may be a novel therapeutic intervention to prevent plasma leakage in dengue.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Meta.Michels@radboudumc.nl.
authors.forename: Meta
authors.initials: M
authors.lastname: Michels
authors.affiliation: Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Japtok
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors.forename: Bachti
authors.initials: B
authors.lastname: Alisjahbana
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors.forename: Rudi
authors.initials: R
authors.lastname: Wisaksana
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors.forename: Uun
authors.initials: U
authors.lastname: Sumardi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, Bandung, Indonesia.
authors.forename: Mita
authors.initials: M
authors.lastname: Puspita
authors.affiliation: Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D000075243:Apolipoproteins M; D002199:Capillary Permeability; D003715:Dengue / Q000097:blood* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007214:Indonesia; D054834:Lipocalins / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D010949:Plasma; D010976:Platelet Count; D011446:Prospective Studies; D019595:Severe Dengue / Q000097:blood* / Q000503:physiopathology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D054834:Lipocalins; D008074:Lipoproteins; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: APOM protein; Blood platelets; Dengue; Human; Sphingosine 1-phosphate