title: Immunohistochemical detection of sphingosine-1-phosphate receptor 1 and 5 in human multiple sclerosis lesions.
abstract: OBJECTIVE
  Sphingosine-1-phosphate receptor (S1PR) modulating therapies are currently in the clinic or undergoing investigation for multiple sclerosis (MS) treatment. However, the expression of S1PRs is still unclear in the central nervous system under normal conditions and during neuroinflammation.
  
  
  METHODS
  Using immunohistochemistry we examined tissues from both grey and white matter MS lesions for sphingosine-1-phosphate receptor 1 (S1P1 ) and 5 (S1P5 ) expression. Tissues from Alzheimer's disease (AD) cases were also examined.
  
  
  RESULTS
  S1P1 expression was restricted to astrocytes and endothelial cells in control tissues and a decrease in endothelial cell expression was found in white matter MS lesions. In grey matter MS lesions, astrocyte expression was lost in active lesions, while in quiescent lesions it was restored to normal expression levels. CNPase colocalization studies demonstrated S1P5 expression on myelin and both were reduced in demyelinated lesions. In AD tissues we found no difference in S1P1 expression.
  
  
  CONCLUSIONS
  These data demonstrate a differential modulation of S1PRs in MS lesions, which may have an impact on S1PR-directed therapies.
authors.affiliation: Merck Serono, Multiple Sclerosis Platform, Geneva, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Brana
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Frossard
authors.forename: Rosanna
authors.initials: R
authors.lastname: Pescini Gobert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Martinier
authors.forename: Ursula
authors.initials: U
authors.lastname: Boschert
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Seabrook
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D066128:Gray Matter / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D000081025:Sphingosine-1-Phosphate Receptors; D066127:White Matter / Q000378:metabolism
chemical_list: D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors
keywords: S1P receptor 1 (S1P1); S1P receptor 5 (S1P5); astrocyte; endothelial cell; multiple sclerosis (MS); sphingosine 1-phosphate (S1P)