Tissue distribution of factor VIII gene expression in vivo - A closer look

Previous studies have shown that factor VIII (FVIII) is expressed by multip le tissues. However, little is known about its cellular ori.-in or its leve l of expression in different organs. In the present study, we examined FVII I gene expression in different tissues on a quantitative basis. Most of the tissues, especially liver and kidney, expressed high levels of FVIII mRNA compared to their level of expression of other hemostatic proteins, includi ng von Willebrand factor (WVF). This was unexpected since FVIII is a trace protein. In situ hybridization analysis confirmed that liver and kidney wer e rich in FVIII mRNA. In the liver, a clear hybridization signal was detect ed in cells lining the sinusoids. FVIII mRNA analysis of purified liver cel ls confirmed the expression of FVIII mRNA by sinusoidal endothelial cells a nd Kupffer cells. Low but significant levels of FVIII mRNA were also detect ed in the hepatocytes. VWF mRNA was not detectable in these cells. Similarl y, immunohistochemical staining of liver tissue revealed that FVIII protein is primarily associated with sinusoidal cells. VWF protein was predominant ly located in the endothelium of larger vessels. In the kidney, FVIII synth esis was localized to the glomeruli and to tubular epithelial cells. Taken together, these results suggest that besides hepatocytes, non-parenchymal c ells (e.g. sinusoidal endothelial cells) contribute to FVIII synthesis. VWF synthesis is primarily confined to extra-hepatic tissues.