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Tumor Necrosis Factor/Cachectin and the Modulation of Endothelial Cell Coagulant Properties

  • David M. Stern
  • Peter P. Nawroth
Conference paper
Part of the Veröffentlichungen aus der Geomedizinischen Forschungsstelle der Heidelberger Akademie der Wissenschaften book series (HD AKAD, volume 1987/88 / 1987/4)

Abstract

The coagulation mechanism is an effector system capable of rapidly and effectively responding to environmental stimuli. In order to play an integral role in the host response in pathophysiologic states, function of the coagulation mechanism must be linked to the host defense. Since the coagulation mechanism is regulated by tonically active, opposing anticoagulant and procoagulant mechanisms, this suggested the following hypothesis: in homeostasis the balance of coagulation mechanisms on the endothelial cell surface should favor anticoagulation, whereas in stimulated states procoagulant activities would predominate. Sepsis, a disease state with multiple abnormalities of intravascular coagulation, provided an opportunity to test this hypothesis. Our question concerned whether a central mediator of the septic state (1,2), Tumor Necrosis Factor/Cachectin (TNF), could induce the coordinate induction of endothelial cell pro-coagulant activity and suppression of anticoagulant mechanism.

Keywords

Tissue Factor Procoagulant Activity Bovine Aortic Endothelial Cell Endothelial Cell Surface Endothelial Cell Monolayer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Beutler B, Cerami A: Cachectin and Tumor Necrosis Factor as two sides of the same biological coin. Nature 320: 584–588, 1986.PubMedCrossRefGoogle Scholar
  2. 2.
    Beutler B, Milsark IW, Cerami AC: Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effects of endotoxin. Science 225: 869–871, 1985.CrossRefGoogle Scholar
  3. 3.
    Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern DM: Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin I. J. Exp. Med. 163: 1363–1375, 1986.PubMedCrossRefGoogle Scholar
  4. 4.
    Lomedico PT, Kilian PL, Gubler V, Stern A, Chizzonite R: Molecular biology of interleukin 1. Cold Spring Harbor Laboratory Symposia on Quantitative Biology, Vol 51: Molecular Biology of Homo Sapiens. 1986 (in press) Google Scholar
  5. 5.
    Stern DM, Bank I, Nawroth PP, Cassimeris J, Kisiel W, Fenton JW, Dinarello C, Chess L, Jaffe EA: Self-regulation of procoagulant events on the endothelial cell surface. J. Exp. Med. 162/1223–1235, 1985.Google Scholar
  6. 6.
    Libby P, Ordovas JM, Auger KR, Robbins AH, Biringi LK, Dinarello LA: Endotoxin and tumor necrosis factor induce interleukin 1 gene expression in adult human vascular endothelial cells. Am. J. Pathol. 124: 179–185, 1986.PubMedGoogle Scholar
  7. 7.
    Nawroth PP, Stern DM: Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J. Exp. Med. 164: 740–743, 1986.CrossRefGoogle Scholar
  8. 8.
    Stern DM, Nawroth P, Handley D, Kisiel W: An endothelial cell dependent pathway of coagulation. Proc. Natl. Acad. Sci. USA 82: 2523–2527, 1985.PubMedCrossRefGoogle Scholar
  9. 9.
    Stern DM, Drillings M, Nossel HL, LaLama KS: Binding of factors IX and IXa to cultured vascular endothelium. Proc. Natl. Acad. Sci. USA 80: 4119–4123, 1983.PubMedCrossRefGoogle Scholar
  10. 10.
    Stern DM, Nawroth PP, Kisiel W, Vehat G, Esmon CT: The binding of factor IXa to cultured bovine aortic endothelial cells: Induction of a specific site in the presence of factors VIII and X. J. Biol. Chem. 260: 6717–6722, 1985.PubMedGoogle Scholar
  11. 11.
    Rimon S, Savion N, Nawroth P, Stern DM: The endothelial factor IX binding site involves a cell surface protein. Blood 66: 367a, 1985.Google Scholar
  12. 12.
    Rodgers GH, Shuman MA: Prothombin is activated on vascular endothelial cells by factor Xa and calcium. Proc. Natl. Acad. Sci. USA 80: 7001–7005, 1983.PubMedCrossRefGoogle Scholar
  13. 13.
    Kadish ZK, Butterfield CE, Folkman J: The effect of fibrin on cultured vascular endothelial cells. Tissue Cell 11: 99–108, 1979.PubMedCrossRefGoogle Scholar
  14. 14.
    Fair DS, Marlar RA, Urin EJ: Human endothelial cells synthesize protein S. Blood 67: 1168–1171, 1986.PubMedGoogle Scholar
  15. 15.
    Stern D, Brett J, Harris K, Nawroth P: Participation of endothelial cells in the protein C - protein S anticoagulant pathway: The synthesis and release of protein S. J. Cell Biol. 102/1971–1978, 1986.PubMedCrossRefGoogle Scholar
  16. 16.
    Stern DM, Nawroth PP, Harris K, Esmon CT: Cultured bovine aortic endothelial cells promote activated protein C, protein mediated inactivation of factor Va. J. Biol. Chem. 261: 713–718, 1986.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • David M. Stern
    • 1
  • Peter P. Nawroth
    • 1
  1. 1.Thrombosis/Hematology Reserach ProgramOklahoma Medical Reserach FoundationOklahoma CityUSA

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