The 55-kD tumor necrosis factor receptor and CD95 independently signal murine hepatocyte apoptosis and subsequent liver failure (original) (raw)

Abstract

BACKGROUND: Activation of either the 55-kD tumor necrosis factor receptor (TNF-R1) or CD95 (Fas/Apo-1) causes apoptosis of cells and liver failure in mice, and has been associated with human liver disorders. The aim of this study was first to clarify the association between CD95 activation, hepatocyte apoptosis, and fulminant liver failure. Next, we investigated whether TNF-R1 and CD95 operate independently of each other in the induction of hepatocyte apoptosis. MATERIALS AND METHODS: Using both mice and primary liver cell cultures deficient in either TNF-R1 or functional CD95, the induction of apoptosis and hepatocyte death following activation of TNF-R1 or CD95 were studied in vitro and in various in vivo models of acute liver failure. RESULTS: In vivo or in vitro stimulation of CD95 caused apoptosis of wild-type (wt) murine hepatocytes which had not been sensitized by blocking transcription. Time course studies showed that DNA fragmentation and chromatin condensation preceded, respectively, membrane lysis in vitro and necrosis in vivo. Similar results were obtained after CD95 activation in hepatocytes or livers lacking TNF-R1. Conversely, hepatocytotoxicity due to endogenous or exogenous TNF was not affected in animals or liver cell cultures lacking the expression of functional CD95. CONCLUSIONS: TNF-R1 and CD95 are independent and differentially regulated triggers of murine apoptotic liver failure.

109

Images in this article

Selected References

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

  1. Adachi Y., Bradford B. U., Gao W., Bojes H. K., Thurman R. G. Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology. 1994 Aug;20(2):453–460. [PubMed] [Google Scholar]
  2. Barriault C., Audet M., Yousef I. M., Tuchweber B. Effect of agents which modify reticuloendothelial system function on acute phalloidin-induced lethality and hepatotoxicity in mice. Toxicol Appl Pharmacol. 1995 Apr;131(2):206–215. doi: 10.1006/taap.1995.1063. [DOI] [PubMed] [Google Scholar]
  3. Beutler B., Grau G. E. Tumor necrosis factor in the pathogenesis of infectious diseases. Crit Care Med. 1993 Oct;21(10 Suppl):S423–S435. [PubMed] [Google Scholar]
  4. Boldin M. P., Mett I. L., Varfolomeev E. E., Chumakov I., Shemer-Avni Y., Camonis J. H., Wallach D. Self-association of the "death domains" of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects. J Biol Chem. 1995 Jan 6;270(1):387–391. doi: 10.1074/jbc.270.1.387. [DOI] [PubMed] [Google Scholar]
  5. Brakebusch C., Nophar Y., Kemper O., Engelmann H., Wallach D. Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. EMBO J. 1992 Mar;11(3):943–950. doi: 10.1002/j.1460-2075.1992.tb05133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chatenoud L., Ferran C., Bach J. F. The anti-CD3-induced syndrome: a consequence of massive in vivo cell activation. Curr Top Microbiol Immunol. 1991;174:121–134. doi: 10.1007/978-3-642-50998-8_9. [DOI] [PubMed] [Google Scholar]
  7. Clement M. V., Stamenkovic I. Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions. J Exp Med. 1994 Aug 1;180(2):557–567. doi: 10.1084/jem.180.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cleveland J. L., Ihle J. N. Contenders in FasL/TNF death signaling. Cell. 1995 May 19;81(4):479–482. doi: 10.1016/0092-8674(95)90068-3. [DOI] [PubMed] [Google Scholar]
  9. Czaja M. J., Xu J., Ju Y., Alt E., Schmiedeberg P. Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. Hepatology. 1994 May;19(5):1282–1289. [PubMed] [Google Scholar]
  10. Edwards M. J., Keller B. J., Kauffman F. C., Thurman R. G. The involvement of Kupffer cells in carbon tetrachloride toxicity. Toxicol Appl Pharmacol. 1993 Apr;119(2):275–279. doi: 10.1006/taap.1993.1069. [DOI] [PubMed] [Google Scholar]
  11. Espevik T., Nissen-Meyer J. A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J Immunol Methods. 1986 Dec 4;95(1):99–105. doi: 10.1016/0022-1759(86)90322-4. [DOI] [PubMed] [Google Scholar]
  12. Gantner F., Leist M., Jilg S., Germann P. G., Freudenberg M. A., Tiegs G. Tumor necrosis factor-induced hepatic DNA fragmentation as an early marker of T cell-dependent liver injury in mice. Gastroenterology. 1995 Jul;109(1):166–176. doi: 10.1016/0016-5085(95)90282-1. [DOI] [PubMed] [Google Scholar]
  13. Gantner F., Leist M., Lohse A. W., Germann P. G., Tiegs G. Concanavalin A-induced T-cell-mediated hepatic injury in mice: the role of tumor necrosis factor. Hepatology. 1995 Jan;21(1):190–198. doi: 10.1016/0270-9139(95)90428-x. [DOI] [PubMed] [Google Scholar]
  14. Gilles P. N., Guerrette D. L., Ulevitch R. J., Schreiber R. D., Chisari F. V. HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon-gamma. Hepatology. 1992 Sep;16(3):655–663. doi: 10.1002/hep.1840160308. [DOI] [PubMed] [Google Scholar]
  15. Grell M., Krammer P. H., Scheurich P. Segregation of APO-1/Fas antigen- and tumor necrosis factor receptor-mediated apoptosis. Eur J Immunol. 1994 Oct;24(10):2563–2566. doi: 10.1002/eji.1830241045. [DOI] [PubMed] [Google Scholar]
  16. Hashimoto S., Ishii A., Yonehara S. The E1b oncogene of adenovirus confers cellular resistance to cytotoxicity of tumor necrosis factor and monoclonal anti-Fas antibody. Int Immunol. 1991 Apr;3(4):343–351. doi: 10.1093/intimm/3.4.343. [DOI] [PubMed] [Google Scholar]
  17. Hiramatsu N., Hayashi N., Katayama K., Mochizuki K., Kawanishi Y., Kasahara A., Fusamoto H., Kamada T. Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C. Hepatology. 1994 Jun;19(6):1354–1359. [PubMed] [Google Scholar]
  18. Ishiyama H., Ogino K., Hobara T. Role of Kupffer cells in rat liver injury induced by diethyldithiocarbamate. Eur J Pharmacol. 1995 Jan 13;292(2):135–141. doi: 10.1016/0926-6917(95)90005-5. [DOI] [PubMed] [Google Scholar]
  19. Itoh N., Nagata S. A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. J Biol Chem. 1993 May 25;268(15):10932–10937. [PubMed] [Google Scholar]
  20. Itoh N., Tsujimoto Y., Nagata S. Effect of bcl-2 on Fas antigen-mediated cell death. J Immunol. 1993 Jul 15;151(2):621–627. [PubMed] [Google Scholar]
  21. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  22. Kobayashi N., Hamamoto Y., Yamamoto N., Ishii A., Yonehara M., Yonehara S. Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9620–9624. doi: 10.1073/pnas.87.24.9620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kriegler M., Perez C., DeFay K., Albert I., Lu S. D. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988 Apr 8;53(1):45–53. doi: 10.1016/0092-8674(88)90486-2. [DOI] [PubMed] [Google Scholar]
  24. Laskin D. L., Gardner C. R., Price V. F., Jollow D. J. Modulation of macrophage functioning abrogates the acute hepatotoxicity of acetaminophen. Hepatology. 1995 Apr;21(4):1045–1050. [PubMed] [Google Scholar]
  25. Laskin D. L. Nonparenchymal cells and hepatotoxicity. Semin Liver Dis. 1990 Nov;10(4):293–304. doi: 10.1055/s-2008-1040485. [DOI] [PubMed] [Google Scholar]
  26. Lehmann V., Freudenberg M. A., Galanos C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987 Mar 1;165(3):657–663. doi: 10.1084/jem.165.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Leist M., Gantner F., Bohlinger I., Germann P. G., Tiegs G., Wendel A. Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-alpha requires transcriptional arrest. J Immunol. 1994 Aug 15;153(4):1778–1788. [PubMed] [Google Scholar]
  28. Leist M., Gantner F., Bohlinger I., Tiegs G., Germann P. G., Wendel A. Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol. 1995 May;146(5):1220–1234. [PMC free article] [PubMed] [Google Scholar]
  29. Leist M., Gantner F., Jilg S., Wendel A. Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release. J Immunol. 1995 Feb 1;154(3):1307–1316. [PubMed] [Google Scholar]
  30. Mariani S. M., Matiba B., Armandola E. A., Krammer P. H. The APO-1/Fas (CD95) receptor is expressed in homozygous MRL/lpr mice. Eur J Immunol. 1994 Dec;24(12):3119–3123. doi: 10.1002/eji.1830241231. [DOI] [PubMed] [Google Scholar]
  31. Miethke T., Duschek K., Wahl C., Heeg K., Wagner H. Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST-1. Eur J Immunol. 1993 Jul;23(7):1494–1500. doi: 10.1002/eji.1830230715. [DOI] [PubMed] [Google Scholar]
  32. Miethke T., Wahl C., Heeg K., Echtenacher B., Krammer P. H., Wagner H. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J Exp Med. 1992 Jan 1;175(1):91–98. doi: 10.1084/jem.175.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mizuhara H., O'Neill E., Seki N., Ogawa T., Kusunoki C., Otsuka K., Satoh S., Niwa M., Senoh H., Fujiwara H. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. J Exp Med. 1994 May 1;179(5):1529–1537. doi: 10.1084/jem.179.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Morimoto H., Yonehara S., Bonavida B. Overcoming tumor necrosis factor and drug resistance of human tumor cell lines by combination treatment with anti-Fas antibody and drugs or toxins. Cancer Res. 1993 Jun 1;53(11):2591–2596. [PubMed] [Google Scholar]
  35. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  36. Nagaki M., Muto Y., Ohnishi H., Yasuda S., Sano K., Naito T., Maeda T., Yamada T., Moriwaki H. Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the superantigen staphylococcal enterotoxin B. Gastroenterology. 1994 Feb;106(2):450–458. doi: 10.1016/0016-5085(94)90604-1. [DOI] [PubMed] [Google Scholar]
  37. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  38. Ni R., Tomita Y., Matsuda K., Ichihara A., Ishimura K., Ogasawara J., Nagata S. Fas-mediated apoptosis in primary cultured mouse hepatocytes. Exp Cell Res. 1994 Dec;215(2):332–337. doi: 10.1006/excr.1994.1349. [DOI] [PubMed] [Google Scholar]
  39. Nolan J. P. Intestinal endotoxins as mediators of hepatic injury--an idea whose time has come again. Hepatology. 1989 Nov;10(5):887–891. doi: 10.1002/hep.1840100523. [DOI] [PubMed] [Google Scholar]
  40. Oberhammer F., Bursch W., Parzefall W., Breit P., Erber E., Stadler M., Schulte-Hermann R. Effect of transforming growth factor beta on cell death of cultured rat hepatocytes. Cancer Res. 1991 May 1;51(9):2478–2485. [PubMed] [Google Scholar]
  41. Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B. C. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 1992 May 25;267(15):10709–10715. [PubMed] [Google Scholar]
  42. Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., Itoh N., Suda T., Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature. 1993 Aug 26;364(6440):806–809. doi: 10.1038/364806a0. [DOI] [PubMed] [Google Scholar]
  43. Pfeffer K., Matsuyama T., Kündig T. M., Wakeham A., Kishihara K., Shahinian A., Wiegmann K., Ohashi P. S., Krönke M., Mak T. W. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993 May 7;73(3):457–467. doi: 10.1016/0092-8674(93)90134-c. [DOI] [PubMed] [Google Scholar]
  44. Rothe J., Lesslauer W., Lötscher H., Lang Y., Koebel P., Köntgen F., Althage A., Zinkernagel R., Steinmetz M., Bluethmann H. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature. 1993 Aug 26;364(6440):798–802. doi: 10.1038/364798a0. [DOI] [PubMed] [Google Scholar]
  45. Rouvier E., Luciani M. F., Golstein P. Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity. J Exp Med. 1993 Jan 1;177(1):195–200. doi: 10.1084/jem.177.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Schulze-Osthoff K., Krammer P. H., Dröge W. Divergent signalling via APO-1/Fas and the TNF receptor, two homologous molecules involved in physiological cell death. EMBO J. 1994 Oct 3;13(19):4587–4596. doi: 10.1002/j.1460-2075.1994.tb06780.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schwall R. H., Robbins K., Jardieu P., Chang L., Lai C., Terrell T. G. Activin induces cell death in hepatocytes in vivo and in vitro. Hepatology. 1993 Aug;18(2):347–356. doi: 10.1016/0270-9139(93)90018-i. [DOI] [PubMed] [Google Scholar]
  48. Seglen P. O. Preparation of rat liver cells. 3. Enzymatic requirements for tissue dispersion. Exp Cell Res. 1973 Dec;82(2):391–398. doi: 10.1016/0014-4827(73)90357-1. [DOI] [PubMed] [Google Scholar]
  49. Smith R. A., Baglioni C. The active form of tumor necrosis factor is a trimer. J Biol Chem. 1987 May 25;262(15):6951–6954. [PubMed] [Google Scholar]
  50. Song H. Y., Dunbar J. D., Donner D. B. Aggregation of the intracellular domain of the type 1 tumor necrosis factor receptor defined by the two-hybrid system. J Biol Chem. 1994 Sep 9;269(36):22492–22495. [PubMed] [Google Scholar]
  51. Steininger R., Roth E., Függer R., Winkler S., Längle F., Grünberger T., Götzinger P., Sautner T., Mühlbacher F. Transhepatic metabolism of TNF-alpha, IL-6, and endotoxin in the early hepatic reperfusion period after human liver transplantation. Transplantation. 1994 Jul 27;58(2):179–183. [PubMed] [Google Scholar]
  52. Suda T., Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med. 1994 Mar 1;179(3):873–879. doi: 10.1084/jem.179.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
  54. Tanaka M., Suda T., Takahashi T., Nagata S. Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 1995 Mar 15;14(6):1129–1135. doi: 10.1002/j.1460-2075.1995.tb07096.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Tartaglia L. A., Ayres T. M., Wong G. H., Goeddel D. V. A novel domain within the 55 kd TNF receptor signals cell death. Cell. 1993 Sep 10;74(5):845–853. doi: 10.1016/0092-8674(93)90464-2. [DOI] [PubMed] [Google Scholar]
  56. Tartaglia L. A., Rothe M., Hu Y. F., Goeddel D. V. Tumor necrosis factor's cytotoxic activity is signaled by the p55 TNF receptor. Cell. 1993 Apr 23;73(2):213–216. doi: 10.1016/0092-8674(93)90222-c. [DOI] [PubMed] [Google Scholar]
  57. Tewari M., Dixit V. M. Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. J Biol Chem. 1995 Feb 17;270(7):3255–3260. doi: 10.1074/jbc.270.7.3255. [DOI] [PubMed] [Google Scholar]
  58. Tiegs G., Wolter M., Wendel A. Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem Pharmacol. 1989 Feb 15;38(4):627–631. doi: 10.1016/0006-2952(89)90208-6. [DOI] [PubMed] [Google Scholar]
  59. Watanabe-Fukunaga R., Brannan C. I., Itoh N., Yonehara S., Copeland N. G., Jenkins N. A., Nagata S. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol. 1992 Feb 15;148(4):1274–1279. [PubMed] [Google Scholar]
  60. Westendorp M. O., Frank R., Ochsenbauer C., Stricker K., Dhein J., Walczak H., Debatin K. M., Krammer P. H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995 Jun 8;375(6531):497–500. doi: 10.1038/375497a0. [DOI] [PubMed] [Google Scholar]
  61. Wong G. H., Goeddel D. V. Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. J Immunol. 1994 Feb 15;152(4):1751–1755. [PubMed] [Google Scholar]
  62. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
  63. Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989 May 1;169(5):1747–1756. doi: 10.1084/jem.169.5.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]