See also Tuddenham E. Far away and long ago. This issue, pp 34–5.
Human liver sinusoidal endothelial cells but not hepatocytes contain factor VIII
Article first published online: 9 JAN 2014
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 12, Issue 1, pages 36–42, January 2014
How to Cite
Human liver sinusoidal endothelial cells but not hepatocytes contain factor VIII. J Thromb Haemost 2014; 12: 36–42., , , , , , .
Manuscript handled by: P. H. Reitsma
Final decision: P. H. Reitsma, 13 September 2013
- Issue published online: 9 JAN 2014
- Article first published online: 9 JAN 2014
- Accepted manuscript online: 30 SEP 2013 09:12AM EST
- Manuscript Received: 15 APR 2013
- Flemish Research Foundation. Grant Numbers: G.0231.05, G.0275.05
- KU Leuven Wyeth and Baxter Chairs for Hemophilia
- Professor Norbert Heimburger Chair for Thrombosis and Hemostasis (KU Leuven)
- Excellentie Financiering KU Leuven. Grant Number: EF/05/013
- Programma Financiering KU Leuven. Grant Number: PF/10/014
- coagulation factor VIII;
- endothelial cells;
- hemophilia A;
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.
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.
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.
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.
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.