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. 1989 May;134(5):1087–1097.

Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis.

T A Drake 1, J H Morrissey 1, T S Edgington 1
PMCID: PMC1879887  PMID: 2719077

Abstract

Tissue factor (TF), the primary cellular initiator of the coagulation protease cascade, is implicated in having important roles in hemostasis, thrombogenesis, inflammation, and the cellular immune response, although the cytologic distribution of TF in tissues has yet to be described. This study used epitope-defined monoclonal antibodies to human tissue factor for immunohistochemical localization of TF in normal human tissues. TF was selectively expressed in tissues and was associated with cells rather than extracellular matrix. It was anatomically sequestered from blood, being undetectable in endothelium and peripheral blood cells. TF was present in vascular adventitia, organ capsules, epidermis, and mucosal epithelium. Most dermal and submucosal fibroblasts were negative. Except for alveolar macrophages and possibly dendritic cells of some lymphoid follicles, tissue macrophages did not express TF; (expression was demonstrable in LPS stimulated monocytes). Cerebral cortex, renal glomeruli, and cardiac myocytes were additional sites of prominent TF expression. Based on the cellular distribution of TF, it is hypothesized that intravascular initiation of coagulation requires induced expression by intravascular cells, and that the normal distribution of TF represents a hemostatic "envelope" ready to activate coagulation when vascular integrity is disrupted.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bevilacqua M. P., Pober J. S., Majeau G. R., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med. 1984 Aug 1;160(2):618–623. doi: 10.1084/jem.160.2.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Majeau G. R., Fiers W., Cotran R. S., Gimbrone M. A., Jr Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4533–4537. doi: 10.1073/pnas.83.12.4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Broze G. J., Jr, Warren L. A., Novotny W. F., Higuchi D. A., Girard J. J., Miletich J. P. The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood. 1988 Feb;71(2):335–343. [PubMed] [Google Scholar]
  5. Colucci M., Balconi G., Lorenzet R., Pietra A., Locati D., Donati M. B., Semeraro N. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest. 1983 Jun;71(6):1893–1896. doi: 10.1172/JCI110945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Conkling P. R., Greenberg C. S., Weinberg J. B. Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. Blood. 1988 Jul;72(1):128–133. [PubMed] [Google Scholar]
  7. Cybulsky M. I., Chan M. K., Movat H. Z. Acute inflammation and microthrombosis induced by endotoxin, interleukin-1, and tumor necrosis factor and their implication in gram-negative infection. Lab Invest. 1988 Apr;58(4):365–378. [PubMed] [Google Scholar]
  8. Drake T. A., Rodgers G. M., Sande M. A. Tissue factor is a major stimulus for vegetation formation in enterococcal endocarditis in rabbits. J Clin Invest. 1984 Jun;73(6):1750–1753. doi: 10.1172/JCI111383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dvorak H. F., Senger D. R., Dvorak A. M., Harvey V. S., McDonagh J. Regulation of extravascular coagulation by microvascular permeability. Science. 1985 Mar 1;227(4690):1059–1061. doi: 10.1126/science.3975602. [DOI] [PubMed] [Google Scholar]
  10. Edwards R. L., Rickles F. R., Bobrove A. M. Mononuclear cell tissue factor: cell of origin and requirements for activation. Blood. 1979 Aug;54(2):359–370. [PubMed] [Google Scholar]
  11. Fisher K. L., Gorman C. M., Vehar G. A., O'Brien D. P., Lawn R. M. Cloning and expression of human tissue factor cDNA. Thromb Res. 1987 Oct 1;48(1):89–99. doi: 10.1016/0049-3848(87)90349-5. [DOI] [PubMed] [Google Scholar]
  12. Geczy C. L., Meyer P. A. Leukocyte procoagulant activity in man: an in vitro correlate of delayed-type hypersensitivity. J Immunol. 1982 Jan;128(1):331–336. [PubMed] [Google Scholar]
  13. Gown A. M., Vogel A. M., Gordon D., Lu P. L. A smooth muscle-specific monoclonal antibody recognizes smooth muscle actin isozymes. J Cell Biol. 1985 Mar;100(3):807–813. doi: 10.1083/jcb.100.3.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gregory S. A., Edgington T. S. Tissue factor induction in human monocytes. Two distinct mechanisms displayed by different alloantigen-responsive T cell clones. J Clin Invest. 1985 Dec;76(6):2440–2445. doi: 10.1172/JCI112260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guesdon J. L., Ternynck T., Avrameas S. The use of avidin-biotin interaction in immunoenzymatic techniques. J Histochem Cytochem. 1979 Aug;27(8):1131–1139. doi: 10.1177/27.8.90074. [DOI] [PubMed] [Google Scholar]
  16. Gurney E. G., Harrison R. O., Fenno J. Monoclonal antibodies against simian virus 40 T antigens: evidence for distinct sublcasses of large T antigen and for similarities among nonviral T antigens. J Virol. 1980 Jun;34(3):752–763. doi: 10.1128/jvi.34.3.752-763.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hedner U., Kisiel W. Use of human factor VIIa in the treatment of two hemophilia A patients with high-titer inhibitors. J Clin Invest. 1983 Jun;71(6):1836–1841. doi: 10.1172/JCI110939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Helin H., Edgington T. S. Allogeneic induction of the human T cell-instructed monocyte procoagulant response is rapid and is elicited by HLA-DR. J Exp Med. 1983 Sep 1;158(3):962–975. doi: 10.1084/jem.158.3.962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Heyderman E., Neville A. M. A shorter immunoperoxidase technique for the demonstration of carcinoembryonic antigen and other cell products. J Clin Pathol. 1977 Feb;30(2):138–140. doi: 10.1136/jcp.30.2.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hopper K. E., Geczy C. L., Davies W. A. A mechanism of migration inhibition in delayed-type hypersensitivity reactions. I. Fibrin deposition on the surface of elicited peritoneal macrophages on vivo. J Immunol. 1981 Mar;126(3):1052–1058. [PubMed] [Google Scholar]
  21. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  22. Kadish J. L., Wenc K. M., Dvorak H. F. Tissue factor activity of normal and neoplastic cells: quantitation and species specificity. J Natl Cancer Inst. 1983 Mar;70(3):551–557. [PubMed] [Google Scholar]
  23. Levy G. A., Leibowitz J. L., Edgington T. S. Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice. J Exp Med. 1981 Oct 1;154(4):1150–1163. doi: 10.1084/jem.154.4.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lusher J. M., Shapiro S. S., Palascak J. E., Rao A. V., Levine P. H., Blatt P. M. Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: a multicenter therapeutic trial. N Engl J Med. 1980 Aug 21;303(8):421–425. doi: 10.1056/NEJM198008213030803. [DOI] [PubMed] [Google Scholar]
  25. Marlar R. A., Kleiss A. J., Griffin J. H. An alternative extrinsic pathway of human blood coagulation. Blood. 1982 Dec;60(6):1353–1358. [PubMed] [Google Scholar]
  26. Maynard J. R., Dreyer B. E., Stemerman M. B., Pitlick F. A. Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts. Blood. 1977 Sep;50(3):387–396. [PubMed] [Google Scholar]
  27. Morrissey J. H., Fair D. S., Edgington T. S. Monoclonal antibody analysis of purified and cell-associated tissue factor. Thromb Res. 1988 Nov 1;52(3):247–261. doi: 10.1016/0049-3848(88)90084-9. [DOI] [PubMed] [Google Scholar]
  28. Morrissey J. H., Fakhrai H., Edgington T. S. Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell. 1987 Jul 3;50(1):129–135. doi: 10.1016/0092-8674(87)90669-6. [DOI] [PubMed] [Google Scholar]
  29. Morrissey J. H., Revak D., Tejada P., Fair D. S., Edgington T. S. Resolution of monomeric and heterodimeric forms of tissue factor, the high-affinity cellular receptor for factor VII. Thromb Res. 1988 May 15;50(4):481–493. doi: 10.1016/0049-3848(88)90197-1. [DOI] [PubMed] [Google Scholar]
  30. Nemerson Y., Bach R. Tissue factor revisited. Prog Hemost Thromb. 1982;6:237–261. [PubMed] [Google Scholar]
  31. Nemerson Y. Tissue factor and hemostasis. Blood. 1988 Jan;71(1):1–8. [PubMed] [Google Scholar]
  32. Rivers R. P., Hathaway W. E., Weston W. L. The endotoxin-induced coagulant activity of human monocytes. Br J Haematol. 1975 Jul;30(3):311–316. doi: 10.1111/j.1365-2141.1975.tb00547.x. [DOI] [PubMed] [Google Scholar]
  33. Rodgers G. M., Greenberg C. S., Shuman M. A. Characterization of the effects of cultured vascular cells on the activation of blood coagulation. Blood. 1983 Jun;61(6):1155–1162. [PubMed] [Google Scholar]
  34. Rodgers G. M. Hemostatic properties of normal and perturbed vascular cells. FASEB J. 1988 Feb;2(2):116–123. doi: 10.1096/fasebj.2.2.3277885. [DOI] [PubMed] [Google Scholar]
  35. Scarpati E. M., Wen D., Broze G. J., Jr, Miletich J. P., Flandermeyer R. R., Siegel N. R., Sadler J. E. Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry. 1987 Aug 25;26(17):5234–5238. doi: 10.1021/bi00391a004. [DOI] [PubMed] [Google Scholar]
  36. Spicer E. K., Horton R., Bloem L., Bach R., Williams K. R., Guha A., Kraus J., Lin T. C., Nemerson Y., Konigsberg W. H. Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5148–5152. doi: 10.1073/pnas.84.15.5148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tannenbaum S. H., Finko R., Cines D. B. Antibody and immune complexes induce tissue factor production by human endothelial cells. J Immunol. 1986 Sep 1;137(5):1532–1537. [PubMed] [Google Scholar]
  38. Tipping P. G., Dowling J. P., Holdsworth S. R. Glomerular procoagulant activity in human proliferative glomerulonephritis. J Clin Invest. 1988 Jan;81(1):119–125. doi: 10.1172/JCI113282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Weiss H. J., Lages B. Evidence for tissue factor-dependent activation of the classic extrinsic coagulation mechanism in blood obtained from bleeding time wounds. Blood. 1988 Mar;71(3):629–635. [PubMed] [Google Scholar]
  40. Wood G. S., Warnke R. Suppression of endogenous avidin-binding activity in tissues and its relevance to biotin-avidin detection systems. J Histochem Cytochem. 1981 Oct;29(10):1196–1204. doi: 10.1177/29.10.7028859. [DOI] [PubMed] [Google Scholar]

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