Evidence that the Human Hepatocyte Contain and Secrete Factor VIII
Human factor VIII (procoagulant: VIII:C, coagulant antigen: VIII:Ag) is a hetero-dimeric plasma protein consisting of 80 kDa and 90–120 kDa polypeptides linked by divalent metal-ion bridges. In plasma F. VIII circulates non-covalently bound to von Willebrand factor. In spite of recent advances in biochemistry of F. VIII, the specific cellular origin of this protein is still obscure. In the past, several animal studies have failed to clearly indicate the organ most important for F. VIII production (Review 1). Recently it was shown that liver transplantation to a haemophilia A patient resulted in normalization of plasma VIII:C . The molecular cloning of human factor VIII was performed using A DNA library from human liver . Two attempts to demonstrate VIII: Ag in liver tissue biopsies gave inconsistent results, although the same monoclonal antibody was used. In the first study  VIII: Ag immune reactivity was disclosed to liver sinusoideal lining cells, whereas the second study  demonstrated VIII: Ag in endoplasmatic reticulum of hepatocytes, the site of protein synthesis, but some VIII:Ag reactivity was also seen in sinusoideal cells. It therefore is reasonably assumed that F. VIII synthesis takes place in the liver. The present investigation, performed on isolated and cultivated human hepatocytes, indicates that the hepatocyte is a production site for F. VIII.
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