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. 1997 Mar;150(3):873–880.

Tissue factor initiates glomerular fibrin deposition and promotes major histocompatibility complex class II expression in crescentic glomerulonephritis.

J H Erlich 1, S R Holdsworth 1, P G Tipping 1
PMCID: PMC1857877  PMID: 9060825

Abstract

Increased glomerular tissue factor (TF) expression is associated with glomerular fibrin deposition and renal failure in human and experimental crescentic glomerulonephritis (GN). However, the in vivo functional contribution of TF to the development of glomerular fibrin deposition, crescent formation, and renal failure in GN has not been established. The contribution of TF to fibrin deposition and renal injury was studied in a rabbit model of crescentic GN in which glomerular macrophage infiltration, augmented TF expression, and fibrin deposition are prominent. Administration of anti-TF antibody inhibited glomerular TF activity in nephritic glomeruli by 96%, without affecting macrophage accumulation or systemic indices of coagulation. Anti-TF antibody significantly reduced glomerular fibrin deposition (fibrin scores, 0.43 +/- 0.10 (treated) and 1.40 +/- 0.19 (control); P < 0.0005), crescent formation (0.33 +/- 0.05 (treated) and 1.0 +/- 0.06 (control); P < 0.0005), and development of renal failure (serum creatinine, 168 +/- 22 mumol/l (treated) and 267 +/- 35 mumol/l (control); P < 0.04). This was associated with significant reduction in proteinuria (1189 +/- 277 mg/24 hours (treated) and 2060 +/- 336 mg/24 hours (control); P < 0.03) and expression of MHC class II antigen in glomeruli (1.25 +/- 0.41 (treated) and 2.83 +/- 0.53 (control); P < 0.03) and in tubules and interstitial areas. These data demonstrate that TF is the major in vivo initiator of fibrin deposition in crescentic GN. The reduction in proteinuria and glomerular major histocompatibility class II antigen expression by TF inhibition suggests that TF may also activate other mediators that contribute to glomerular injury.

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Selected References

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  1. Border W. A., Wilson C. B., Dixon F. J. Failure of heparin to affect two types of experimental glomerulonephritis in rabbits. Kidney Int. 1975 Sep;8(3):140–148. doi: 10.1038/ki.1975.93. [DOI] [PubMed] [Google Scholar]
  2. Boyce N. W., Tipping P. G., Holdsworth S. R. Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis. Kidney Int. 1989 Mar;35(3):778–782. doi: 10.1038/ki.1989.52. [DOI] [PubMed] [Google Scholar]
  3. Bromberg M. E., Konigsberg W. H., Madison J. F., Pawashe A., Garen A. Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8205–8209. doi: 10.1073/pnas.92.18.8205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Broze G. J., Jr, Likert K., Higuchi D. Inhibition of factor VIIa/tissue factor by antithrombin III and tissue factor pathway inhibitor. Blood. 1993 Sep 1;82(5):1679–1681. [PubMed] [Google Scholar]
  5. Broze G. J., Jr The role of tissue factor pathway inhibitor in a revised coagulation cascade. Semin Hematol. 1992 Jul;29(3):159–169. [PubMed] [Google Scholar]
  6. Cook H. T., Smith J., Salmon J. A., Cattell V. Functional characteristics of macrophages in glomerulonephritis in the rat. O2- generation, MHC class II expression, and eicosanoid synthesis. Am J Pathol. 1989 Feb;134(2):431–437. [PMC free article] [PubMed] [Google Scholar]
  7. Crutchley D. J., Conanan L. B., Que B. G. K+ channel blockers inhibit tissue factor expression by human monocytic cells. Circ Res. 1995 Jan;76(1):16–20. doi: 10.1161/01.res.76.1.16. [DOI] [PubMed] [Google Scholar]
  8. Drake T. A., Morrissey J. H., Edgington T. S. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol. 1989 May;134(5):1087–1097. [PMC free article] [PubMed] [Google Scholar]
  9. Dziadek M., Clements R., Mitrangas K., Reiter H., Fowler K. Analysis of degradation of the basement membrane protein nidogen, using a specific monoclonal antibody. Eur J Biochem. 1988 Feb 15;172(1):219–225. doi: 10.1111/j.1432-1033.1988.tb13876.x. [DOI] [PubMed] [Google Scholar]
  10. Eldredge C., Merritt S., Goyal M., Kulaga H., Kindt T. J., Wiggins R. Analysis of T cells and major histocompatibility complex class I and class II mRNA and protein content and distribution in antiglomerular basement membrane disease in the rabbit. Am J Pathol. 1991 Nov;139(5):1021–1035. [PMC free article] [PubMed] [Google Scholar]
  11. Erlich J. H., Apostolopoulos J., Wun T. C., Kretzmer K. K., Holdsworth S. R., Tipping P. G. Renal expression of tissue factor pathway inhibitor and evidence for a role in crescentic glomerulonephritis in rabbits. J Clin Invest. 1996 Jul 15;98(2):325–335. doi: 10.1172/JCI118796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fleck R. A., Rao L. V., Rapaport S. I., Varki N. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. Thromb Res. 1990 Jul 15;59(2):421–437. doi: 10.1016/0049-3848(90)90148-6. [DOI] [PubMed] [Google Scholar]
  13. Holdsworth S. R., Tipping P. G. Macrophage-induced glomerular fibrin deposition in experimental glomerulonephritis in the rabbit. J Clin Invest. 1985 Oct;76(4):1367–1374. doi: 10.1172/JCI112112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Imamura T., Iyama K., Takeya M., Kambara T., Nakamura S. Role of macrophage tissue factor in the development of the delayed hypersensitivity reaction in monkey skin. Cell Immunol. 1993 Dec;152(2):614–622. doi: 10.1006/cimm.1993.1317. [DOI] [PubMed] [Google Scholar]
  15. Kincaid-Smith P. Coagulation and renal disease. Kidney Int. 1972 Oct;2(4):183–190. doi: 10.1038/ki.1972.93. [DOI] [PubMed] [Google Scholar]
  16. Lena P., Freyria A. M., Lyon M., Cadoré J. L., Guiguen F., Greenland T., Belleville J., Cordier G., Mornex J. F. Increased expression of tissue factor mRNA and procoagulant activity in ovine lentivirus-infected alveolar macrophages. Res Virol. 1994 May-Aug;145(3-4):209–214. doi: 10.1016/s0923-2516(07)80024-0. [DOI] [PubMed] [Google Scholar]
  17. Levi M., ten Cate H., Bauer K. A., van der Poll T., Edgington T. S., Büller H. R., van Deventer S. J., Hack C. E., ten Cate J. W., Rosenberg R. D. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest. 1994 Jan;93(1):114–120. doi: 10.1172/JCI116934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Liotta L. A., Goldfarb R. H., Brundage R., Siegal G. P., Terranova V., Garbisa S. Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res. 1981 Nov;41(11 Pt 1):4629–4636. [PubMed] [Google Scholar]
  19. Lobel S. A., Knight K. L. The role of rabbit Ia molecules in immune functions as determined with the use of an anti-Ia monoclonal antibody. Immunology. 1984 Jan;51(1):35–43. [PMC free article] [PubMed] [Google Scholar]
  20. Luther T., Flössel C., Mackman N., Bierhaus A., Kasper M., Albrecht S., Sage E. H., Iruela-Arispe L., Grossmann H., Ströhlein A. Tissue factor expression during human and mouse development. Am J Pathol. 1996 Jul;149(1):101–113. [PMC free article] [PubMed] [Google Scholar]
  21. Malliaros J., Holdsworth S. R., Wojta J., Erlich J., Tipping P. G. Glomerular fibrinolytic activity in anti-GBM glomerulonephritis in rabbits. Kidney Int. 1993 Sep;44(3):557–564. doi: 10.1038/ki.1993.281. [DOI] [PubMed] [Google Scholar]
  22. Mayer U., Zimmermann K., Mann K., Reinhardt D., Timpl R., Nischt R. Binding properties and protease stability of recombinant human nidogen. Eur J Biochem. 1995 Feb 1;227(3):681–686. doi: 10.1111/j.1432-1033.1995.tb20188.x. [DOI] [PubMed] [Google Scholar]
  23. McCluskey R. T., Vassalli P., Gallo G., Baldwin D. S. An immunofluorescent study of pathogenic mechanisms in glomerular diseases. N Engl J Med. 1966 Mar 31;274(13):695–701. doi: 10.1056/NEJM196603312741301. [DOI] [PubMed] [Google Scholar]
  24. McVey J. H. Tissue factor pathway. Baillieres Clin Haematol. 1994 Sep;7(3):469–484. doi: 10.1016/s0950-3536(05)80094-0. [DOI] [PubMed] [Google Scholar]
  25. Mueller B. M., Reisfeld R. A., Edgington T. S., Ruf W. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11832–11836. doi: 10.1073/pnas.89.24.11832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Naish P., Penn G. B., Evans D. J., Peters D. K. The effect of defibrination on nephrotoxic serum nephritis in rabbits. Clin Sci. 1972 May;42(5):643–646. doi: 10.1042/cs0420643. [DOI] [PubMed] [Google Scholar]
  27. Neale T. J., Tipping P. G., Carson S. D., Holdsworth S. R. Participation of cell-mediated immunity in deposition of fibrin in glomerulonephritis. Lancet. 1988 Aug 20;2(8608):421–424. doi: 10.1016/s0140-6736(88)90413-8. [DOI] [PubMed] [Google Scholar]
  28. Nemerson Y. Tissue factor: then and now. Thromb Haemost. 1995 Jul;74(1):180–184. [PubMed] [Google Scholar]
  29. Rapaport S. I., Rao L. V. The tissue factor pathway: how it has become a "prima ballerina". Thromb Haemost. 1995 Jul;74(1):7–17. [PubMed] [Google Scholar]
  30. Taylor F. B., Jr, Chang A., Ruf W., Morrissey J. H., Hinshaw L., Catlett R., Blick K., Edgington T. S. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock. 1991 Mar;33(3):127–134. [PubMed] [Google Scholar]
  31. Thomson N. M., Moran J., Simpson I. J., Peters D. K. Defibrination with ancrod in nephrotoxic nephritis in rabbits. Kidney Int. 1976 Nov;10(5):343–347. doi: 10.1038/ki.1976.120. [DOI] [PubMed] [Google Scholar]
  32. Thomson N. M., Simpson I. J., Peters D. K. A quantitative evaluation of anticoagulants in experimental nephrotoxic nephritis. Clin Exp Immunol. 1975 Feb;19(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Tipping P. G., Erlich J. H., Apostolopoulos J., Mackman N., Loskutoff D., Holdsworth S. R. Glomerular tissue factor expression in crescentic glomerulonephritis. Correlations between antigen, activity, and mRNA. Am J Pathol. 1995 Dec;147(6):1736–1748. [PMC free article] [PubMed] [Google Scholar]
  35. Tipping P. G., Holdsworth S. R. The participation of macrophages, glomerular procoagulant activity, and factor VIII in glomerular fibrin deposition. Studies on anti-GBM antibody-induced glomerulonephritis in rabbits. Am J Pathol. 1986 Jul;124(1):10–17. [PMC free article] [PubMed] [Google Scholar]
  36. Tipping P. G., Leong T. W., Holdsworth S. R. Tumor necrosis factor production by glomerular macrophages in anti-glomerular basement membrane glomerulonephritis in rabbits. Lab Invest. 1991 Sep;65(3):272–279. [PubMed] [Google Scholar]
  37. Tipping P. G., Lowe M. G., Holdsworth S. R. Glomerular interleukin 1 production is dependent on macrophage infiltration in anti-GBM glomerulonephritis. Kidney Int. 1991 Jan;39(1):103–110. doi: 10.1038/ki.1991.13. [DOI] [PubMed] [Google Scholar]
  38. Tipping P. G., Thomson N. M., Holdsworth S. R. A comparison of fibrinolytic and defibrinating agents in established experimental glomerulonephritis. Br J Exp Pathol. 1986 Aug;67(4):481–491. [PMC free article] [PubMed] [Google Scholar]
  39. Tipping P. G., Worthington L. A., Holdsworth S. R. Quantitation and characterization of glomerular procoagulant activity in experimental glomerulonephritis. Lab Invest. 1987 Feb;56(2):155–159. [PubMed] [Google Scholar]
  40. Wiggins R. C., Glatfelter A., Brukman J. Procoagulant activity in glomeruli and urine of rabbits with nephrotoxic nephritis. Lab Invest. 1985 Aug;53(2):156–165. [PubMed] [Google Scholar]
  41. Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]
  42. Zhang Y., Deng Y., Luther T., Müller M., Ziegler R., Waldherr R., Stern D. M., Nawroth P. P. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest. 1994 Sep;94(3):1320–1327. doi: 10.1172/JCI117451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zivelin A., Rao L. V., Rapaport S. I. Evidence for an essential role of tissue factor dependent blood coagulation in the pathogenesis of the local Shwartzman reaction. Blood Cells Mol Dis. 1995;21(1):9–19. doi: 10.1006/bcmd.1995.0003. [DOI] [PubMed] [Google Scholar]
  44. Zivelin A., Rao L. V., Rapaport S. I. Mechanism of the anticoagulant effect of warfarin as evaluated in rabbits by selective depression of individual procoagulant vitamin K-dependent clotting factors. J Clin Invest. 1993 Nov;92(5):2131–2140. doi: 10.1172/JCI116814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zucker S., Conner C., DiMassmo B. I., Ende H., Drews M., Seiki M., Bahou W. F. Thrombin induces the activation of progelatinase A in vascular endothelial cells. Physiologic regulation of angiogenesis. J Biol Chem. 1995 Oct 6;270(40):23730–23738. doi: 10.1074/jbc.270.40.23730. [DOI] [PubMed] [Google Scholar]

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