Download PDF
Thromb Haemost 1988; 59(02): 289-294
DOI: 10.1055/s-0038-1642773
Original Articles
Schattauer GmbH Stuttgart

Factor VIII Procoagulant Antigen in Human Tissues

N Kadhom
1   The Unités 56, Institut National de la Santé et de la Recherche Médicale, Le Kremlin-Bicêtre and Paris, France
,
C Wolfrom
1   The Unités 56, Institut National de la Santé et de la Recherche Médicale, Le Kremlin-Bicêtre and Paris, France
,
M Gautier
1   The Unités 56, Institut National de la Santé et de la Recherche Médicale, Le Kremlin-Bicêtre and Paris, France
,
J P Allain
3   The Centre National de Transfusion Sanguine, Paris, France
,
D Frommel
2   The Unités 56, Institut National de la Santé et de la Recherche Médicale, Le Kremlin-Bicêtre and Paris, France
› Author Affiliations
Further Information

Publication History

Received 07 September 1987

Accepted after revision 21 December 1987

Publication Date:
21 May 2018 (online)

  PDF Download  Permissions and Reprints

Summary

The localization of factor VIII procoagulant antigen (VIII: Ag) and factor VIII von Willebrand antigen (VWF: Ag) was investigated in human liver, lung, spleen, placenta and umbilical cord, by an immunoperoxidase technique using an avidin biotin complex (ABC). Positive staining for VIII: Ag was observed in the endothelial cells of liver sinusoids, veins and arteries, as well as in the endothelial cells of placenta, lung and spleen. VWF: Ag was detected in the vascular endothelial cells of all the organs explored. The staining intensity of both VIII: Ag and VWF: Ag varied in the different tissues and showed a distinctive pattern of distribution in the liver. VIII: Ag was also observed in the cytoplasm of dysplastic, foetal-like hepatocytes which infiltrated one liver specimen. Our results agree with the view that liver endothelial cells are a major site of Factor VIII (F VIII) storage and secondary release into the circulation. However, the bright staining intensity of VIII: Ag and VWF: Ag in the lung and placenta suggests that these two tissues might also be a substantial source of F VIII.

Keywords

Factor VIII - Tissue localization - Immunoenzymohistology
 

  • References

  • 1 Bloom AL, Giddings SI C, Wilks CJ. Factor VIII on the vascular intima: possible importance in hemostasis and thrombosis. Nature New Biol 1972; 241: 217-219
    PubMedGoogle Scholar
  • 2 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest 1973; 52: 2757-2764
    CrossrefPubMedGoogle Scholar
  • 3 Nachman R, Levine R, Jaffe EA. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest 1977; 60: 914-921
    CrossrefPubMedGoogle Scholar
  • 4 Hoyer LW. The factor VIII Complex: structure and function. Blood 1981; 58: 1-13
    PubMedGoogle Scholar
  • 5 Stel HV, van der Kwast ThH, Veerman EC I. Detection of factor VUI/coagulant antigen in human liver tissue. Nature 1983; 303: 530-532
    CrossrefPubMedGoogle Scholar
  • 6 Gitschier J, Wood WI, Goralka TM, Wion KL, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM. Characterization of the human factor VIII gene. Nature 1984; 312: 326-330
    CrossrefPubMedGoogle Scholar
  • 7 Wood WI, Capon DJ, Simonsen CC, Eaton DL, Gitschier J, Keyt B, Seeburg PH, Smith DH, Hollingshead P, Wion KL, Delwart E, Tuddenham EG D, Vehar GA, Lawn RM. Expression of active human factor VIII from recombinant DNA clones. Nature 1984; 312: 330-337
    CrossrefPubMedGoogle Scholar
  • 8 Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC, Amphlett GW, Foster WB, Coe ML, Knutson GJ, Fass DN, Hewick RM. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature 1984; 312: 342-347
    CrossrefPubMedGoogle Scholar
  • 9 Lewis JH, Bontempo FA, Spero JA, Ragni MV, Starzl TE. Liver transplantation in a hemophiliac. N Engl J Med 1985; 312: 1189-1190
    PubMedGoogle Scholar
  • 10 Webster WP, Reddick RL, Roberts HR, Penick GD. Release of factor VIII (antihaemophilic factor) from perfused organs and tissues. Nature 1967; 213: 1146-1147
    CrossrefPubMedGoogle Scholar
  • 11 Veltkamp JJ, Asfaou E, van de Torren K, van der Does JA, van Tilburg NH, Pauwels EK L. Extrahepatic factor VIII synthesis: lung transplants in haemophilic dogs. Transplantation 1974; 18: 56-62
    CrossrefPubMedGoogle Scholar
  • 12 Bloom AL. The biosynthesis of factor VIII. Clinics in Haematology 1979; 8: 53-77
    PubMedGoogle Scholar
  • 13 van der Kwast ThH, Stel HV, Cristen E, Bertina RM, Veerman EC I. Localization of factor VUI-procoagulant antigen: An immunohistological survey of the human body using monoclonal antibodies. Blood 1986; 67: 222-227
    PubMedGoogle Scholar
  • 14 Vehar GA, Keyt B, Eaton D, Rodriquez H, O’Brien DP, Rotblat F, Oppermann H, Keck R, Wood WI, Harkins RN, Tuddenham EG D, Lawn RM, Capon DJ. Structure of human factor VIII. Nature 1984; 312: 337-342
    CrossrefPubMedGoogle Scholar
  • 15 Wion KL, Kelly D, Summerfield JA, Tuddenham EG D, Lawn RM. Distribution of factor VIII mRNA and antigen in human liver and other tissues. Nature 1985; 317: 726-729
    CrossrefPubMedGoogle Scholar
  • 16 Frommel D, Allain JP, Courouce AM, Derose S, Trepo D, Crivelli O, Rizzetto M. Long-lasting abatement of HbsAg synthesis induced by acute delta infection. Lancet 1983; 1: 656-657
    PubMedGoogle Scholar
  • 17 Croissant MP, van de Pol H, Lee HH, Allain JP. Characterization of four monoclonal antibodies to factor VIII coagulant protein and their use in immunopurification of factor VIII. Thromb Haemostas 1986; 56: 271-276
    PubMedGoogle Scholar
  • 18 Goodall AH, Meyer D. Registry of monoclonal antibodies to factor VIII and von Willebrand factor. Thromb Haemostas 1985; 54: 878-891
    PubMedGoogle Scholar
  • 19 Hsu SM, Braine L, Fanger H. The use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) Procedures. J His- tochem Cytochem 1981; 29: 577-580
    PubMedGoogle Scholar
  • 20 Wilchek M, Bayer EA. The avidin-biotin complex in immunology. Immunol Today 1984; 5: 39-43
    CrossrefPubMedGoogle Scholar
  • 21 Fulcher CA, De Graaf Mahoney S, Roberts JR, Kasper CK, Zimmerman TS. Localization of human factor VIII inhibitor epitopes to two polypeptide fragments. Proc Natl Acad Sci USA 1985; 82: 7728-7732
    CrossrefPubMedGoogle Scholar
  • 22 Zelechowska MG, van Mourik JA, Brodniewicz-Proba T. Ultrastruc- tural localization of factor VIII procoagulant antigen in human liver hepatocytes. Nature 1985; 317: 729-730
    CrossrefPubMedGoogle Scholar
  • 23 Feldmann G. Morphologic aspects of hepatic synthesis and secretion of plasma proteins. In: Progress in liver diseases. Popper H, Schaffner F. (eds) pp 23-40 Grune and Stratton; New York: 1979
    Google Scholar
  • 24 Exner T, Rickard KA, Kronenberg H. Measurement of factor VIII CAg by immunoradiometric assay in human tissue extracts. Thromb Res 1983; 32: 427-436
    CrossrefPubMedGoogle Scholar
  • 25 Maximow AA, Bloom W. A text-book of Histology. pp 435-449 WB Saunders Co; 1957
    Google Scholar
  • 26 Groth CG, Hathaway WE, Gustafsson A, Geis WP, Putnam CW, Bjorken C, Porter KA, Starzl TE. Correction of coagulation in the hemophilic dog by transplantation of lymphatic tissue. Surgery 1974; 75: 725-733
    PubMedGoogle Scholar
  • 27 Buckley PJ, Dickson SA, Walker WS. Human splenic sinusoidal lining cells express antigens associated with monocytes, macrophages, endothelial cells, and T lymphocytes. J Immunol 1985; 134: 2310-2315
    PubMedGoogle Scholar