title: Circulating endothelial cell protein C receptor: endothelial regulation and cumulative impact of gender and A3 haplotype.
abstract: BACKGROUND
  The endothelial cell (EC) protein C receptor (EPCR) negatively regulates coagulation and inflammation. Factors and mechanisms regulating the expression of cell-bound EPCR and the release of soluble (s) EPCR are still unclear.
  
  
  METHODS
  We investigated the reciprocal regulation of membrane-bound and sEPCR upon inflammation using primary cultures of vascular EC. The impact of 2 parameters, gender and EPCR gene A3 haplotype, on sEPCR plasma basal level and endothelial expression was examined by Elisa and flow cytometry.
  
  
  RESULTS
  Exposure of EC to tumor necrosis factor α causes a rapid downregulation of membrane-associated EPCR expression without affecting markedly the spontaneous release of sEPCR by EC. In a cohort of 100 healthy donors, we show that males express significantly higher basal sEPCR in plasma than females (194 ± 12 vs. 145 ± 9 ng/ml, respectively, p<0.01). Both gender and EPCR A3 haplotype affect sEPCR plasma levels but have no apparent effect on EPCR expression by EC. No quantitative correlation between cellular expression and circulating blood sEPCR was observed, suggesting that endothelial expression may not reflect the plasma level.
  
  
  CONCLUSIONS
  Male gender is another parameter with A3 haplotype associated with elevated sEPCR levels in blood, and both parameters may contribute to selective regulatory mechanisms of EPCR release upon inflammation.
authors.affiliation: INSERM UMR643, Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Guitton
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gérard
authors.forename: Thibaut
authors.initials: T
authors.lastname: Quillard
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000235:genetics* / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D000074283:Endothelial Protein C Receptor; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics* / Q000502:physiology; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha