title: Human liver sinusoidal endothelial cells but not hepatocytes contain factor VIII.
abstract: BACKGROUND
  Although the liver is the major site of coagulation factor VIII (FVIII) synthesis, the type of cells producing FVIII within the liver is still unclear.
  
  
  OBJECTIVE
  To measure FVIII in extracts of primary liver sinusoidal endothelial cells (LSECs) and hepatocytes, thereby preventing potential bias resulting from the modifications of the cell phenotype that can take place during in vitro culture.
  
  
  METHODS
  LSECs were purified by flow cytometry cell sorting on the basis of their coexpression of Tie2 and CD32b. The purity of the cells was controlled by RNA sequencing. FVIII activity (FVIII:C) in extracts of purified cells was measured with a sensitive FVIII chromogenic assay, in which the specificity of the reaction is controlled by neutralization of FVIII activity with specific inhibitor antibodies.
  
  
  RESULTS
  The FVIII:C concentration in purified LSECs ranged from 0.3 to 2.8 nU per cell. In contrast, FVIII:C was undetectable in hepatocytes. The intracellular FVIII:C concentrations are therefore at least 10-100-fold higher in LSECs than in hepatocytes.
  
  
  CONCLUSIONS
  Our data demonstrate that LSECs, but not hepatocytes, contain measurable amounts of FVIII:C, and suggest that the former are the main cells producing FVIII in the human liver.
authors.affiliation: Department of Genetics and Molecular Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: T
authors.initials: T
authors.lastname: Shahani
authors.forename: K
authors.initials: K
authors.lastname: Covens
authors.forename: R
authors.initials: R
authors.lastname: Lavend'homme
authors.forename: N
authors.initials: N
authors.lastname: Jazouli
authors.forename: E
authors.initials: E
authors.lastname: Sokal
authors.forename: K
authors.initials: K
authors.lastname: Peerlinck
authors.forename: M
authors.initials: M
authors.lastname: Jacquemin
mesh_terms: D042783:Endothelial Cells / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D005169:Factor VIII
keywords: coagulation factor VIII; endothelial cells; hemophilia A; hepatocytes; liver