Ultrastructural localization of factor VIII procoagulant antigen in human liver hepatocytes

Abstract

Factor VIII is generally believed to circulate in blood as a multimeric complex of two glycoproteins which are physiologically and immunologically distinct. One component of the factor VIII complex is factor VIII procoagulant activity (FVIII:C) which is associated with factor VIII/procoagulant antigen (FVIII:Ag, formerly FVIII/CAg). The second, larger unit of the complex is factor VIII/von Willebrand factor (vWF:Ag, formerly factor VIII-related antigen or FVIIIRAg). FVIII:C has anti-haemophilic activity and is defective or deficient in patients with classical haemophilia, and vWF:Ag is absent in patients with von Willebrand disease^1–3. FVIII:Ag was demonstrated recently in endothelial cells lining hepatic sinusoids, by using immunoperoxidase staining and light microscopy^4,5, whereas biochemical data had indicated its presence predominantly in the hepatocyte fractions and in lesser amounts in endothelial cells^6,7. Moreover, recent hybridization experiments detected FVIII:C messenger RNA in liver⁸ and kidney⁹ tissues. Despite several efforts, the cells responsible for FVIII: C synthesis have not been unequivocally identified. Here we use protein A–gold complex labelling to demonstrate the ultrastructural localization of FVIII:C in human liver cells; the results indicate that hepatocytes may synthesize FVIII:Ag.