Abstract
The cellular site of synthesis of factor VIII (FVIII:C; anti-haemophilic factor) has long been sought1. Previous studies suggested the liver as a major site of synthesis, but extrahepatic sources such as spleen and lung have been implicated2–6. Using an immunoradiometric assay (IRMA), we recently localized factor VIII antigen (FVIII: Ag, formerly FVIII: CAg), to whole perfused guinea pig liver and spleen, and to isolated hepatocytes, with lesser or trace amounts in other tissues7. Using an immunohistological technique, Stel et al.8 detected FVIII: Ag in normal human liver sinusoidal endothelial cells, while Exner et al.9 detected FVIII: Ag by IRMA in extracts of human lymph nodes, lung, liver and spleen. The localization of antigen in tissues does not, however, distinguish sites of factor VIII synthesis from those of storage, and such experiments are subject to misinterpretation due to entrapment of plasma factor VIII in tissues. The recent cloning of the human factor VIII gene10–12 provides hybridization probes for the detection of factor VIII messenger RNA in cells, thus directly determining sites of synthesis. During complementary DNA cloning, we detected factor VIII mRNA in liver10, and it has been localized by others in liver and placenta12 and in liver and kidney13. In the present study, we detected factor VIII mRNA in isolated human hepatocytes, in spleen and in numerous tissues including lymph nodes and kidney, but not in white blood cells or cultured endothelial cells. We also found that the factor VIII, factor VII, factor IX and protein C antigens in liver are predominantly localized in hepatocytes, while very little von Willebrand factor antigen (vWF:Ag, formerly FVIIIRAg) is detectable in this organ.
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Wion, K., Kelly, D., Summerfield, J. et al. Distribution of factor VIII mRNA and antigen in human liver and other tissues. Nature 317, 726–729 (1985). https://doi.org/10.1038/317726a0
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DOI: https://doi.org/10.1038/317726a0
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