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Human liver sinusoidal endothelial cells but not hepatocytes contain FVIII

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Shahani, Tina Covens, Kris Lavend'Homme, Renaud Jazouli, Nawal [UCL] Sokal, Etienne [UCL] Jacquemin, Marc

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. OBJECTIVES: 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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2014
Language Anglais
Journal information "Journal of Thrombosis and Haemostasis" - Vol. 12, no. 1, p. 36-42 (2014)
Peer reviewed yes
Publisher Wiley-Blackwell Publishing Ltd. ((United Kingdom) Oxford)
issn 1538-7933
e-issn 1538-7836
Publication status Publié
Affiliations UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
Keywords coagulation factor VIII ; endothelial cells ; hemophilia A ; hepatocytes ; liver
Links
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Bibliographic reference Shahani, Tina ; Covens, Kris ; Lavend'Homme, Renaud ; Jazouli, Nawal ; Sokal, Etienne ; et. al. Human liver sinusoidal endothelial cells but not hepatocytes contain FVIII. In: Journal of Thrombosis and Haemostasis, Vol. 12, no. 1, p. 36-42 (2014)
Permanent URL http://hdl.handle.net/2078.1/143983