Thromb Haemost 2007; 97(01): 11-14
DOI: 10.1160/TH06-09-0524
Rapid and Short Communication
Schattauer GmbH

Alternatively spliced human tissue factor (asHTF) is not pro-coagulant

Petra Censarek*
1   Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany
,
Anett Bobbe*
1   Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany
,
Maria Grandoch
2   Institut für Pharmakologie, Universität Duisburg-Essen, Universitätsklinikum, Germany
,
Karsten Schrör
1   Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany
,
Artur-Aron Weber
1   Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

Received 15 September 2006

Accepted after revision 14 November 2006

Publication Date:
30 November 2017 (online)

Summary

It has been proposed that alternatively-spliced human tissue factor (asHTF) is pro-coagulant. We have evaluated the function of asHTF in a mammalian expression system. Full-length human tissue factor (HTF) and asHTF were cloned from smooth muscle cells and over-expressed in HEK293 cells. As expected, a marked pro-coagulant activity (FX activation, thrombin generation) was observed on the surface, in lysates, and on microparticles from HTF transfected cells. In contrast, no pro-coagulant activity of as HTF was observed.

* These authors contributed equally.


 
  • References

  • 1 Mackman N, Morrissey JH, Fowler B. et al Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade. Biochemistry 1989; 28: 1755-62.
  • 2 Bogdanov VY, Balasubramanian V, Hathcock J. et al Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 2003; 9: 458-62.
  • 3 Engelmann B, Luther T, Müller I. Intravascular tissue factor pathway – a model for rapid initiation of coagulation within the blood vessel. Thromb Haemost 2003; 89: 3-8.
  • 4 Szotowski B, Antoniak S, Poller W. et al Procoagulant soluble tissue factor is released from endothelial cells in response to inflammatory cytokines. Circ Res 2005; 96: 1233-9.
  • 5 Sturk-Maquelin KN, Niewland R, Momijn FPHTM. et al Pro-and non-coagulant forms of noncell-bound tissue factor in vivo. J Thromb Haemost 2003; 1: 1920-6.
  • 6 Chand HS, Ness SA, Kisiel W. Identification of a novel human tissue factor splice variant that is upregulated in tumor cells. Int J Cancer 2006; 118: 1713-20.
  • 7 Butenas S, Mann KG. Active tissue factor in blood?. Nat Med 2004; 10: 1155-6.
  • 8 Rauch BH, Millette E, Kenagy RD. et al Thrombin-and factor Xa-induced DNA synthesis is mediated by transactivation of fibroblast growth factor receptor-1 in human vascular smooth muscle cells. Circ Res 2004; 94: 340-5.
  • 9 Hemker HC, Giesen P, Al Dieri R. et al Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33: 4-15.
  • 10 Stampfuss JJ, Censarek P, Fischer JW. et al Rapid release of active tissue factor from human arterial smooth muscle cells under flow conditions. Arterioscler Thromb Vasc Biol 2006; 26: e34-7.
  • 11 Szotowski B, Antoniak S, Rauch U. Alternatively spliced tissue factor: a previously unknown piece in the puzzle of hemostasis. Trends Cardiovasc Med 2006; 16: 177-82.
  • 12 Butenas S, Bouchard BA, Brummel-Ziedins KE. et al Tissue factor activity in whole blood. Blood 2005; 105: 2764-70.
  • 13 Bogdanov VY, Kirk RI, Miller C. et al Identification and characterization of murine alternatively spliced tissue factor. J Thromb Haemost 2006; 4: 158-67.
  • 14 Neuenschwander PF, Morrissey JH. Deletion of the membrane anchoring region of tissue factor abolishes autoactivation of factor VII but not cofactor function. J Biol Chem 1992; 267: 14477-82.
  • 15 Morrissey JH, Neuenschwander PF, Huang Q. et al Factor VIIa-tissue factor: Functional importance of protein-membrane interactions. Thromb Haemost 1997; 78: 112-6.
  • 16 Neuenschwander PF, Morrissey JH. Roles of the membrane-interactive regions of factor VIIa and tissue factor. The factor VIIa Gla domain is dispensable for binding to tissue factor but important for activation of factor X. J Biol Chem 1994; 269: 8007-13.
  • 17 Paborsky LR, Caras IW, Fisher KL. et al Lipid association, but not the transmembrane domain, is required for tissue factor activity. J Biol Chem 1991; 266: 21911-21916.
  • 18 Waters EK, Morrissey JH. Restoring full biological activity to the isolated ectodomain of an integral membrane protein. Biochemistry 2006; 45: 3769-74.
  • 19 Rauch U, Antoniak S, Boots M. et al Association of tissue-factor upregulation in squamous-cell carcinoma of the lung with increased tissue factor in circulating blood. Lancet Oncol 2005; 6: 254
  • 20 Greenberg DL, Davie EW. Blood coagulation factors: Their complementary DNAs, genes, and expression. In Hemostasis and Thrombosis. Basic Principles & Clinical Practice. 4 th ed. Lippincott Williams & Wilkins; Philadelphia, USA: 2001: 21-57.