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. 1992 Oct;60(10):4388–4393. doi: 10.1128/iai.60.10.4388-4393.1992

von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells.

N Teysseire 1, D Arnoux 1, F George 1, J Sampol 1, D Raoult 1
PMCID: PMC257476  PMID: 1328057

Abstract

Mediterranean spotted fever, a tick-borne rickettsiosis caused by Rickettsia conorii, may lead to small-vessel or deep-vein thrombosis. In order to evaluate the role of endothelial cell alteration in this lesion, we infected human endothelial cells derived from umbilical veins with R. conorii. We report the induction of two previously unreported prothrombotic mechanisms in rickettsial disease: (i) a progressive decline in thrombomodulin antigen and (ii) early expression of tissue factor, and, as described for R. rickettsii infection, later release of von Willebrand factor from Weibel-Palade bodies. Thrombomodulin expression in infected endothelial cells, measured by the thrombin-dependent activation of protein C or flow cytometric analysis, decreased steadily between 4 and 24 h after inoculation with rickettsiae. R. conorii infection induced tissue factor expression, measured by clotting assay and flow cytometric analysis, which was detectable 2 h postinoculation, reached its maximum 4 h postinoculation, and progressively decreased thereafter. Infection resulted in a relatively late release of von Willebrand factor antigen into the culture medium. A double-label immunofluorescence assay for the simultaneous evaluation of von Willebrand factor and R. conorii showed that the depletion of cytoplasmic von Willebrand factor stored in Weibel-Palade bodies was due to a direct effect of the intracellular R. conorii. These disturbances of endothelial function observed with R. conorii-infected cells may provide a paradigm for the elucidation of thrombotic pathobiology with Mediterranean spotted fever.

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Selected References

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  1. Andoh K., Pettersen K. S., Filion-Myklebust C., Prydz H. Observations on the cell biology of tissue factor in endothelial cells. Thromb Haemost. 1990 Apr 12;63(2):298–302. [PubMed] [Google Scholar]
  2. Bauer K. A., ten Cate H., Barzegar S., Spriggs D. R., Sherman M. L., Rosenberg R. D. Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism of humans. Blood. 1989 Jul;74(1):165–172. [PubMed] [Google Scholar]
  3. 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]
  4. Bruggeman C. A., Debie W. H., Muller A. D., Schutte B., van Dam-Mieras M. C. Cytomegalovirus alters the von Willebrand factor content in human endothelial cells. Thromb Haemost. 1988 Apr 8;59(2):264–268. [PubMed] [Google Scholar]
  5. Conforti G., Zanetti A., Colella S., Abbadini M., Marchisio P. C., Pytela R., Giancotti F., Tarone G., Languino L. R., Dejana E. Interaction of fibronectin with cultured human endothelial cells: characterization of the specific receptor. Blood. 1989 May 1;73(6):1576–1585. [PubMed] [Google Scholar]
  6. Drancourt M., Alessi M. C., Levy P. Y., Juhan-Vague I., Raoult D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by Rickettsia conorii- and Rickettsia rickettsii-infected cultured endothelial cells. Infect Immun. 1990 Aug;58(8):2459–2463. doi: 10.1128/iai.58.8.2459-2463.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Esmon C. T. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem. 1989 Mar 25;264(9):4743–4746. [PubMed] [Google Scholar]
  8. Gerlach H., Esposito C., Stern D. M. Modulation of endothelial hemostatic properties: an active role in the host response. Annu Rev Med. 1990;41:15–24. doi: 10.1146/annurev.me.41.020190.000311. [DOI] [PubMed] [Google Scholar]
  9. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Key N. S., Vercellotti G. M., Winkelmann J. C., Moldow C. F., Goodman J. L., Esmon N. L., Esmon C. T., Jacob H. S. Infection of vascular endothelial cells with herpes simplex virus enhances tissue factor activity and reduces thrombomodulin expression. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7095–7099. doi: 10.1073/pnas.87.18.7095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Latron Y., Alessi M. C., George F., Anfosso F., Poncelet P., Juhan-Vague I. Characterization of epitheloid cells from human omentum: comparison with endothelial cells from umbilical veins. Thromb Haemost. 1991 Sep 2;66(3):361–367. [PubMed] [Google Scholar]
  12. Moore K. L., Andreoli S. P., Esmon N. L., Esmon C. T., Bang N. U. Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest. 1987 Jan;79(1):124–130. doi: 10.1172/JCI112772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nawroth P. P., Stern D. M. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986 Mar 1;163(3):740–745. doi: 10.1084/jem.163.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  15. Poncelet P., Carayon P. Cytofluorometric quantification of cell-surface antigens by indirect immunofluorescence using monoclonal antibodies. J Immunol Methods. 1985 Dec 17;85(1):65–74. doi: 10.1016/0022-1759(85)90274-1. [DOI] [PubMed] [Google Scholar]
  16. Rao A. K., Schapira M., Clements M. L., Niewiarowski S., Budzynski A. Z., Schmaier A. H., Harpel P. C., Blackwelder W. C., Scherrer J. R., Sobel E. A prospective study of platelets and plasma proteolytic systems during the early stages of Rocky Mountain spotted fever. N Engl J Med. 1988 Apr 21;318(16):1021–1028. doi: 10.1056/NEJM198804213181603. [DOI] [PubMed] [Google Scholar]
  17. Raoult D., Drancourt A. M., Ardissone J. P. Enzyme secretion by human endothelial cells infected with Rickettsia conorii. Acta Virol. 1987 Aug;31(4):352–356. [PubMed] [Google Scholar]
  18. Schorer A. E., Moldow C. F., Rick M. E. Interleukin 1 or endotoxin increases the release of von Willebrand factor from human endothelial cells. Br J Haematol. 1987 Oct;67(2):193–197. doi: 10.1111/j.1365-2141.1987.tb02326.x. [DOI] [PubMed] [Google Scholar]
  19. Schorer A. E., Rick P. D., Swaim W. R., Moldow C. F. Structural features of endotoxin required for stimulation of endothelial cell tissue factor production; exposure of preformed tissue factor after oxidant-mediated endothelial cell injury. J Lab Clin Med. 1985 Jul;106(1):38–42. [PubMed] [Google Scholar]
  20. Silverman D. J. Adherence of platelets to human endothelial cells infected by Rickettsia rickettsii. J Infect Dis. 1986 Apr;153(4):694–700. doi: 10.1093/infdis/153.4.694. [DOI] [PubMed] [Google Scholar]
  21. Silverman D. J., Bond S. B. Infection of human vascular endothelial cells by Rickettsia rickettsii. J Infect Dis. 1984 Feb;149(2):201–206. doi: 10.1093/infdis/149.2.201. [DOI] [PubMed] [Google Scholar]
  22. Silverman D. J. Rickettsia rickettsii-induced cellular injury of human vascular endothelium in vitro. Infect Immun. 1984 Jun;44(3):545–553. doi: 10.1128/iai.44.3.545-553.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sporn L. A., Shi R. J., Lawrence S. O., Silverman D. J., Marder V. J. Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies. Blood. 1991 Nov 15;78(10):2595–2602. [PubMed] [Google Scholar]
  24. Van Dam-Mieras M. C., Bruggeman C. A., Muller A. D., Debie W. H., Zwaal R. F. Induction of endothelial cell procoagulant activity by cytomegalovirus infection. Thromb Res. 1987 Jul 1;47(1):69–75. doi: 10.1016/0049-3848(87)90241-6. [DOI] [PubMed] [Google Scholar]
  25. Vicente V., Alberca I., Ruiz R., Herrero I., Gonzalez R., Portugal J. Coagulation abnormalities in patients with Mediterranean spotted fever. J Infect Dis. 1986 Jan;153(1):128–131. doi: 10.1093/infdis/153.1.128. [DOI] [PubMed] [Google Scholar]
  26. Vicente V., España F., Tabernero D., Estellés A., Aznar J., Hendl S., Griffin J. H. Evidence of activation of the protein C pathway during acute vascular damage induced by Mediterranean spotted fever. Blood. 1991 Jul 15;78(2):416–422. [PubMed] [Google Scholar]
  27. Walker D. H., Firth W. T., Edgell C. J. Human endothelial cell culture plaques induced by Rickettsia rickettsii. Infect Immun. 1982 Jul;37(1):301–306. doi: 10.1128/iai.37.1.301-306.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Walker D. H., Gear J. H. Correlation of the distribution of Rickettsia conorii, microscopic lesions, and clinical features in South African tick bite fever. Am J Trop Med Hyg. 1985 Mar;34(2):361–371. doi: 10.4269/ajtmh.1985.34.361. [DOI] [PubMed] [Google Scholar]
  29. Walker D. H., Mattern W. D. Rickettsial vasculitis. Am Heart J. 1980 Dec;100(6 Pt 1):896–906. doi: 10.1016/0002-8703(80)90072-1. [DOI] [PubMed] [Google Scholar]
  30. Walker T. S., Brown J. S., Hoover C. S., Morgan D. A. Endothelial prostaglandin secretion: effects of typhus rickettsiae. J Infect Dis. 1990 Nov;162(5):1136–1144. doi: 10.1093/infdis/162.5.1136. [DOI] [PubMed] [Google Scholar]

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