Skip to main content

Physiological, Immunological, and Pathological Functions of Tumor Necrosis Factor (TNF) Revealed by TNF Receptor-Deficient Mice

  • Chapter
Cytokine Knockouts

Part of the book series: Contemporary Immunology ((CONTIM))

  • 103 Accesses

Abstract

Tumor necrosis factor (TNF) has a long history that goes back well into the last century. It is now a hundred years ago that the surgeon William Coley observed a remission of inoperable tumors in some patients after infusion of bacterial toxins (1,2). Unacceptable side effects, however, and a lack of understanding of how these toxins induced hemorrhages in tumors, prevented the further development and application of this treatment. It was more than 60 years later when O’Malley et al. (3) realized that bacterial toxins acted indirectly by inducing an endogenous factor in the host that caused hemorrhagic necrosis in tumors and was hence later called TNF (4,5).Since then, TNF has attracted a great deal of attention and was found to participate in a vast variety of cellular activities that collectively make it the most pleiotropic cytokine identified so far.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

references

  1. Coley, W. B. (1893) The treatment of malignant tumors by repeated inoculations of erysipelas; with a report of ten original cases. Am. J. Med. Sci. 105, 487–511.

    Article  Google Scholar 

  2. Coley, W. B. (1894) Treatment of inoperable malignant tumors with toxins of erysipelas and the bacillus prodigiosus. Trans. Am. Surg. Assoc. 12, 183–212.

    Google Scholar 

  3. O’Malley, W. E., Achinstein, B., Shear, M. J. (1962) Action of bacterial polysaccharide on tumors. II. Damage of sarcoma 37 by serum of mice treated with Serratia marcescens polysaccharide, and induced tolerance. J. Natl. Cancer. Inst. 29, 1169–1175.

    Google Scholar 

  4. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., and Williamson, B. (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA 175, 3666–3670.

    Article  Google Scholar 

  5. Helson, L., Green, S., Carswell, E., and Old, L. J. (1975) Effect of tumor necrosis factor on cultured human melanoma cells. Nature 258, 731–732.

    Article  PubMed  CAS  Google Scholar 

  6. Smith, C. A., Farrah, T., and Goodwin, R. G. (1994) The TNF receptor super-family of cellular and viral proteins: activation, costimulation, and death. Cell 76, 959–962.

    Article  PubMed  CAS  Google Scholar 

  7. Beutler, B., and van Huffel, C. (1994) Unraveling function in the TNF ligand and receptor families (comment). Science 264, 667–668.

    Article  PubMed  CAS  Google Scholar 

  8. Vandenabeele, P., Declercq, W., Beyaert, R., and Fiers, W. (1995) Two tumour necrosis factor receptors: Structure and function. Trends Cell Biol. 5, 392–399.

    Article  PubMed  CAS  Google Scholar 

  9. Wiley, S. R., Schooley, K., Smolak, P. J., et al. (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.

    Google Scholar 

  10. Engelmann, H., Holtmann, H., Brakebusch, C., Avni, Y. S., Sarov, I., Nophar, Y., Hadas, E., Leitner, O., and Wallach, D. (1990) Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity. J. Biol. Chem. 265, 14497–14504.

    PubMed  CAS  Google Scholar 

  11. Itoh, N., Yonehara, S., Ishii, A., Yonehara, M., Mizushima, S., Sameshima, M., Hase, A., Seto, Y., and Nagata, S. (1991) The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66, 233–243.

    Article  PubMed  CAS  Google Scholar 

  12. Tartaglia, L. A., Ayres, T. M., Wong, G. H., and Goeddel, D. V. (1993) A novel domain within the 55 kd TNF receptor signals cell death. Cell 74, 845–53.

    Article  PubMed  CAS  Google Scholar 

  13. Itoh, N., and Nagata, S. (1993) A novel protein domain required for apoptosis. J. Biol. Chem. 268, 10,932–10, 937.

    Google Scholar 

  14. Wong, G. H. and Goeddel, D. V. (1994) Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. J. Immunol. 152, 1751–1755.

    PubMed  CAS  Google Scholar 

  15. Schulze-Osthoff, K., Krammer, P. H., and Droge, W. (1994) Divergent signalling via APO-1/Fas and the TNF receptor, two homologous molecules involved in physiological cell death. EMBO J. 13, 4587–4596.

    PubMed  CAS  Google Scholar 

  16. Zheng, L., Fisher, G., Miller, R. E., Peschon, J., Lynch, D. H., and Lenardo, M. J. (1995) Induction of apoptosis in mature T cells by tumour necrosis factor. Nature 377, 348–351.

    Article  PubMed  CAS  Google Scholar 

  17. Rousset, F., Garcia, E., and Banchereau, J. (1991) Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J. Exp. Med. 173, 705–710.

    Article  PubMed  CAS  Google Scholar 

  18. Liu, Y. J., Mason, D. Y., Johnson, G. D., Abbot, S., Gregory, C. D., Hardie, D. L., Gordon, J., and MacLennan, I. C. (1991) Germinal center cells express

    Google Scholar 

  19. bc1–2 protein after activation by signals which prevent their entry into apoptosis. Eur. J. Immunol. 21, 1905–10.

    Google Scholar 

  20. Kriegler, M., Perez, C., DeFay, K., Albert, L., and Lu, S. D. (1988) A novel form of TNF/cachectin is a cell surface cytotoxin transmembrane protein: ramifications for the complex physiology of TNF. Cell 53, 45–53.

    Article  PubMed  CAS  Google Scholar 

  21. Grell, M., Douni, E., Wajant, H., Lohden, M., Clauss, M., Maxeiner, B., Georgopoulos, S., Lesslauer, W., Kollias, G., Pfizenmaier, K., et al. (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83, 793–802.

    Article  PubMed  CAS  Google Scholar 

  22. Mohler, K. M., Sleath, P. R., Fitzner, J. N., Cerretti, D. P., Alderson, M., Kerwar, S. S., Torrance, D. S., Otten Evans, C. Greenstreet, T., Weerawarna, K., et al. (1994) Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature 370, 218–220.

    Article  PubMed  CAS  Google Scholar 

  23. Gearing, A. J. H., Beckett, P., Christodoulou, M., Churchill, M., Clements, J., Davidson, A. H., Drummond, A. H., Galloway, W. A., Gilbert, R., Gordon, J. L., Leber, T. M., Mangan, M., Miller, K., Nayee, P., Owen, K., Patel, S., Thomas, W., Wells, G., Wood, L. M., and Woolley, K. (1994) Processing of tumor necrosis factor-a precursor by metalloproteinases. Nature 370, 555–557.

    Article  PubMed  CAS  Google Scholar 

  24. McGeehan, G. M., Becherer, J. D., Jr. Bast, R. C., Boyer, C. M., Champion, B., Connolly, K. M., Conway, J. G., Furdon, P., Karp, S., Kidao, S., McElroy, A. B., Nichols, J., Pryzwansky, K. M., Schoenen, F., Sekut, L., Truesdale, A., Verghese, M., Warner, J. and Ways, J. P. (1994) Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. Nature 370, 558–561.

    Article  PubMed  CAS  Google Scholar 

  25. Loetscher, H., Pan, Y. C., Lahm, H. W., Gentz, R., Brockhaus, M., Tabuchi, H., and Lesslauer, W. (1990) Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 61, 351–359.

    Article  PubMed  CAS  Google Scholar 

  26. Schall, T. J., Lewis, M., Koller, K. J., Lee, A., Rice, G. C., Wong, G. H., Gatanaga, T., Granger, G. A., Lentz, R., Raab, H. et al. (1990) Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 61, 361–370.

    Article  PubMed  CAS  Google Scholar 

  27. Smith, C. A., Davis, T., Anderson, D., Solam, L., Beckmann, M. P., Jerzy, R., Dower, S. K., Cosman, D., and Goodwin, R. G. (1990) A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248, 1019–1023.

    Article  PubMed  CAS  Google Scholar 

  28. Loetscher, H., Stueber, D., Banner, D., Mackay, F., and Lesslauer, W. (1993) Human tumor necrosis factor alpha (TNF alpha) mutants with exclusive specificity for the 55—kDa or 75—kDa TNF receptors. J. Biol. Chem. 268, 26350–26357.

    PubMed  CAS  Google Scholar 

  29. Tartaglia, L. A., Pennica, D., and Goeddel, D. V. (1993) Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J. Biol. Chem. 268, 18,542–18, 548.

    Google Scholar 

  30. Vassalli, P. (1992) The pathophysiology of tumor necrosis factors. Annu. Rev. Immunol. 10, 411–452.

    Article  PubMed  CAS  Google Scholar 

  31. Paul, N. L. and Ruddle, N. H. (1988) Lymphotoxin. Ann. Rev. Immunol. 6, 407–438.

    Article  CAS  Google Scholar 

  32. Browning, J. L., Ngam-ek, A., Lawton, P., DeMarinis, J., Tizard, R., Chow, E. P., Hession, C., O’Brine-Greco, B., Foley, S. F., and Ware, C. F. (1993) Lymphotoxin 13, a novel member of the TNF Family that forms a heteromeric complex with Lymphotoxin on the cell surface. Cell 72, 847–856.

    Article  PubMed  CAS  Google Scholar 

  33. Crowe, P. D., VanArsdale, T. L., Walter, B. N., Ware, C. F., Hession, C., Ehrenfels, B., Browning, J., Din, W. S., Goodwin, R. G., and Smith, C. A. (1994) A lymphotoxin-(3—specific receptor. Science 264, 707–710.

    Google Scholar 

  34. De Togni, P., Goellner, J., Ruddle, N. H., Streeter, P. R., Fick, A., Mariathasan, S., Smith, S. C., Carlson, R., Shornick, L. P., Strauss-Schoenberger, J., Russell, J. H., Karr, R., and Chaplin. D. D. (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin (see comments). Science 264, 703–707.

    Article  PubMed  Google Scholar 

  35. Eugster, H. P., Müller, M., Car, B. D., Karrer, U., Schnyder, B., Eng, V. M., Woerly, G., Aguet, M., Zinkernagel, R., Bluethmann, H., and Ryffel, B. (1996) Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice. Int. Immunol. 8, 23–36.

    Article  PubMed  CAS  Google Scholar 

  36. Hohmann, H. P., Brockhaus, M., Baeuerle, P., Remy, R., Kolbeck, R., van Loon, A. (1990) Expression of the types A and B tumor necrosi factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-KB. J. Biol. Chem. 265, 22,409–22, 417.

    Google Scholar 

  37. Rothe, J., Bluethmann, H., Gentz, R., Lesslauer, W., Steinmetz, M. (1993) Genomic organization and promoter function of the murine tumor necrosis factor receptor beta gene. Mol. Immunol. 30, 165–175.

    Article  PubMed  CAS  Google Scholar 

  38. Ohsawa, T. and Natori, S. (1989) Expression of tumor necrosis factor at a specific developmental stage of mouse embryos. Dev. Biol. 135, 459–461.

    Article  PubMed  CAS  Google Scholar 

  39. Hunt, J. S., Chen, H. L., Hu, X. L., Chen, T. Y., and Morrison, D. C. (1992) Tumor necrosis factor-alpha gene expression in the tissues of normal mice. Cytokine 4, 340–346.

    Article  PubMed  CAS  Google Scholar 

  40. Parr, E. L., Chen, H. L., Parr, M. B., and Hunt, J. S. (1995) Synthesis and granular localization of tumor necrosis factor-alpha in activated NK cells in the pregnant mouse uterus. J. Reprod. Immunol. 28, 31–40.

    Article  PubMed  CAS  Google Scholar 

  41. Rothe, J., Lesslauer, W., Lotscher, H., Lang, Y., Koebel, P., Kontgen, F., Althage, A., Zinkernagel, R., Steinmetz, M., and Bluethmann, H (1993) Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364, 798–802.

    Article  PubMed  CAS  Google Scholar 

  42. Pfeffer, K., Matsuyama, T., Kundig, T. M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P. S., Krönke, M., and Mak, T. W. (1993) Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73, 457–467.

    Article  PubMed  CAS  Google Scholar 

  43. Erickson, S. L., de Sauvage, F. J., Kikly, K., Carver Moore, K., Pitts Meek, S., Gillett, N., Sheehan, K. C., Schreiber, R. D., Goeddel, D. V., and Moore. M. W. (1994) Decreased sensitivity to turnour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice. Nature 372, 560–563.

    Article  PubMed  CAS  Google Scholar 

  44. Giroir, B. P., Brown, T., and Beutler, B. (1992) Constitutive synthesis of tumor necrosis factor in the thymus. Proc. Natl. Acad. Sci. USA 89, 4864–4868.

    Article  PubMed  CAS  Google Scholar 

  45. de Kossodo, S., Grau, G. E., Daneva, T., Pointaire, P., Fossati, L., Ody, C., Zapf, J., Piguet, P. F., Gaillard, R. C., and Vassalli, P. (1992) Tumor necrosis factor a is involved in mouse growth and lymphoid tissue development. J. Exp. Med. 176, 1259–1264.

    Article  PubMed  CAS  Google Scholar 

  46. Ranges, G. E., Zlotnik, A., Espevik, T., Dinarello, C. A., Cerami, A., Palladino, M. A. J. (1988) Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J. Exp. Med. 167, 1472–1478.

    Article  PubMed  CAS  Google Scholar 

  47. Zuniga Pflucker, J. C., Di, J., and Lenardo, M. J. (1995) Requirement for TNF-alpha and IL-1 alpha in fetal thymocyte commitment and differentiation. Science 268, 1906–1909.

    Article  PubMed  CAS  Google Scholar 

  48. Zhang, Y., Harada, A., Bluethmann, H., Wang, J. B., Nakao, S., Mukaida, N., and Matsushima, K. (1995) Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: Increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro. Blood 86, 2930–2937.

    PubMed  CAS  Google Scholar 

  49. Slordal, L., Warren, D. J., and Moore, M. A. (1990) Protective effects of tumor necrosis factor on murine hematopoiesis during cycle-specific cytotoxic chemotherapy. Cancer Res. 50, 4216–4220.

    PubMed  CAS  Google Scholar 

  50. Le Hir, M., Bluethmann, H., Kosco-Vilbois, M. H., Müller, M., di Padova, F., Moore, M., Ryffel, B., and Eugster, H.-P. (1996) Differentiation of follicular dendritic cells (FDC) and full antibody responses require TNF receptor-1 (TNFR1) signalling. J. Exp. Med. 183, 2367–2372.

    Article  PubMed  Google Scholar 

  51. Matsumoto, M., Marithasan, S., Nahm, M. H., Baranyay, F., Peschon, J. J., Chaplin, D. D. (1996) Role of Lymphotoxin and the type I TNF receptor in the formation of germinal centers. Science 271, 1289–1291.

    Article  PubMed  CAS  Google Scholar 

  52. Müller, M., Eugster, H. P., Le Hir, M., Shakov, A., Di Padova, F., Maurer, C., Quesniaux, V., and Ryffel, B. (1996) Correction or transfer of the TNF/LTadeficient phenotype by bone marrow transplantation. Mol. Med. 2, 247–255.

    PubMed  Google Scholar 

  53. Nakane, A. (1992) TNF in Listeriosis, in Tumor Necrosis Factor: The Molecules and their Emerging Role in Medicine. ( Beutler B, ed.), Raven, New York, pp. 285–292.

    Google Scholar 

  54. Havell, E. A. (1987) Production of tumor necrosis factor during murine listeriosis. J. Immunol. 139, 4225–4231.

    PubMed  CAS  Google Scholar 

  55. Nakane, A., Minagawa, T., Yasuda, I., Yu, C., and Kato, K. (1988) Prevention by gamma interferon of fatal infection with Listeria monocytogenes in mice treated with cyclosporin A. Infect. Immun. 56, 2011–2015.

    PubMed  CAS  Google Scholar 

  56. Hauser, T., Frei, K., Zinkernagel, R. M., Leist, T. P. (1990) Role of tumor necrosis factor in Listeria resistance of nude mice. Med. Microbiol. Immunol. (Berl) 179, 95–104.

    Article  CAS  Google Scholar 

  57. Buchmeier, N. A., and Schreiber, R. D. (1985) Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc. Natl. Acad. Sci. USA 82, 7404–7408.

    Article  PubMed  CAS  Google Scholar 

  58. Bancroft, G. J., Schreiber, R. D., Bosma, G. C., Bosma, M. J., and Unanue, E. R. (1987) A T cell-independent mechanism of macrophage activation by interferon-gamma J. Immunol. 139, 1104–1107.

    PubMed  CAS  Google Scholar 

  59. Huang, S., Hendriks, W., Althage, A., Hemmi, S., Bluethmann, H., Kamijo, R., Vilcek, J., Zinkernagel, R. M., and Aguet, M. (1993) Immune response in mice that lack the interferon-gamma receptor (see comments). Science 259, 1742–1745.

    Article  PubMed  CAS  Google Scholar 

  60. Flynn, J. L., Goldstein, M. M., Chan, J., Triebold, K. J., Pfeffer, K., Lowenstein, C. J., Schreiber, R., Mak, T. W., and Bloom, B. R. (1995) Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561–572.

    Article  PubMed  CAS  Google Scholar 

  61. Kamijo, R., Le, J., Shapiro, D., Havell, E. A., Huang, S., Aguet, M., Bosland, M., and Vilcek, J. (1993) Mice that lack the interferon-y receptor have profoundly altered responses to infection with Bacillus Calmette-Guerin and subsequent challenge with lipopolysaccharide. J. Exp. Med. 178, 1435–40.

    Article  PubMed  CAS  Google Scholar 

  62. Alexander, J., Jebbari, H., Bluethmann, H., Satoskar, A., and Roberts, C. W. (1996) Immunological control of Toxoplasma gondii and appropriate vaccine design. Curr. Topics Immunol. Microbiol. 219, 183–195.

    CAS  Google Scholar 

  63. Nussler, A. K., and Billiar, T. R. (1993) InfJlammation, immunoregulation, and inducible nitric oxide synthetase. J. Leukoc. Biol. 54, 171–178.

    PubMed  CAS  Google Scholar 

  64. Bluethmann, H., Rothe, J., Schultze, N., Tkachuk, M., and Koebel, P. (1994) Establishment of the role of IL-6 and TNF receptor 1 using gene knockout mice. J. Leukoc. Biol. 56, 565–570.

    PubMed  CAS  Google Scholar 

  65. Kamijo, R., Shapiro, D., Le, J., Huang, S., Aguet, M., and Vilcek, J. (1993) Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon y receptor. Proc. Natl. Acad. Sci. USA 90, 6626–6630.

    Article  PubMed  CAS  Google Scholar 

  66. Trinchieri, G. (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 13, 251–276.

    Article  PubMed  CAS  Google Scholar 

  67. D Andrea, A., Rengaraju, M., Valiante, N. M., Chehimi, J., Kubin, M., Aste, M., Chan, S. H., Kobayashi, M., Young, D., Nickbarg, E., et al. (1992) Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J. Exp. Med. 176, 1387–1398.

    Article  PubMed  Google Scholar 

  68. Chan, S. H., Perussia, B., Gupta, J. W., Kobayashi, M., Pospisil, M., Young, H. A., Wolf, S. F., Young, D., Clark, S. C., and Trinchieri, G. (1991) Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J. Exp. Med. 173, 869–879.

    Article  PubMed  CAS  Google Scholar 

  69. Gazzinelli, R. T., Hieny, S., Wynn, T., Wolf. S., and Sher, A. (1993) IL-12 is required for the T-cell independent induction of IFN-y by an intracellular parasite and induces resistance in T-deficient hosts. Proc. Natl. Acad. Sci. USA 90, 6115–6119.

    Google Scholar 

  70. Tripp, C. S., Gately, M. K., Hakimi, J., Ling, P., and Unanue, E. R. (1994) Neutralization of IL-12 decreases resistance. to Listeria in SCID and C.B-17 mice. Reversal by IFN-gamma. J. Immunol. 152, 1883–1887.

    PubMed  CAS  Google Scholar 

  71. Farrar, M. A., and Schreiber, R. D. (1993) The molecular cell biology of interferon-y and its receptor. Annu. Rev. Immunol. 11, 571–611.

    Article  PubMed  CAS  Google Scholar 

  72. Beutler, B., Milsark, I. W., and Cerami, A. C. (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229, 869–871.

    Article  PubMed  CAS  Google Scholar 

  73. Tracey, K. J., Beutler, B., Lowry, S.F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., Shires, G. T., and Cerami, A. (1986) Shock and tissue injury induced by recompinant human cachectin. Science 234, 470–474.

    Article  PubMed  CAS  Google Scholar 

  74. Morrison, D. C., and Ryan, J. L. (1987) Endotoxin and disease mechanisms. Annu. Rev. Med. 38, 417–432.

    Article  PubMed  CAS  Google Scholar 

  75. Miethke, T., Wahl, C., Heeg, K., Echtenacher, B., Krammer, P. H., and Wagner, H. (1992) T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J. Exp. Med. 175, 91–98.

    Article  PubMed  CAS  Google Scholar 

  76. Waage, A., and Espevik, T. (1988) Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J. Exp. Med. 167, 1987–1992.

    Article  PubMed  CAS  Google Scholar 

  77. Galanos, C., Freudenberg, M. A., and Reutter, W. (1979) Galactosamineinduced sensitisation to the lethal effects of endotoxin. Proc. Natl. Acad. Sci. USA 76, 5939–5943.

    Article  PubMed  CAS  Google Scholar 

  78. Tiegs, G., Wolter, M., and Wendel, A. (1989) Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem. Pharmacol. 38, 627–631.

    Article  PubMed  CAS  Google Scholar 

  79. Bahrami, S., Redl, H., Leichtfeld, G., Yu, Y., and Schlag, G. (1994) Similar cytokine but different coagulation responses to lipopolysaccharide injection in D-galactosamine-sensitized vs nonsensitized rats. Infect. Immunol. 62, 99.

    CAS  Google Scholar 

  80. Decker, K. and Keppler, D. (1974) Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev. Physiol. Biochem. Pharmacol. 71, 77.

    Article  PubMed  CAS  Google Scholar 

  81. Leist, M., Gantner, F., Bohlinger, I., Germann, P. G., Tiegs, G. and Wendel, A. (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNFalpha requires transcriptional arrest. J. Immunol. 153, 1778–1788.

    PubMed  CAS  Google Scholar 

  82. Leist, M., Gantner, F., Jilg, S., and Wendel, A. (1995) Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release. J. Immunol. 154, 1307–1316.

    PubMed  CAS  Google Scholar 

  83. Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., Salfeld, J. et al. (1995) Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80, 401–411.

    Article  PubMed  CAS  Google Scholar 

  84. Xu, H., Gonzalo, J. A., St Pierre, Y., Williams, I. R., Kupper, T. S., Cotran, R. S., Springer, T. A., and Gutierrez Ramos, J. C. (1994) Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. J. Exp. Med. 180, 95–109.

    Article  PubMed  CAS  Google Scholar 

  85. Tartaglia, L. A., Rothe, M., Hu, Y. F., and Goeddel, D. V. (1993) Tumor necrosis factor’s cytotoxic activity is signaled by the p55 TNF receptor. Cell 73, 213–216.

    Article  PubMed  CAS  Google Scholar 

  86. Leist, M., Gantner, F., Künstle, G., Bohlinger, I., Tiegs, G., Bluethmann, H., and Wendel, A. (1996) The 55 kDa tumor necrosis factor receptor and CD95 (fas) independently signal murine hepatocyte apoptosis and subsequent liver failure. Mol. Med. 2, 109–124.

    PubMed  CAS  Google Scholar 

  87. Zhou, T., Edwards, C. K., Yang, P., Wang, Z., Bluethmann, H., and Mountz, J. D. (1996) Greatly accelerated lymphadenopathy and autoimmune disease in 1pr mice lacking tumor necrosis factor receptor 1. J. Immunol. 156, 2661–2665.

    PubMed  CAS  Google Scholar 

  88. Jacob, C. 0. (1992) Studies on the role of tumor necrosis factor in murine and human autoimmunity. J. Autoimmun. 5 (Suppll A), 133–143.

    Article  PubMed  Google Scholar 

  89. Feldmann, M., Brennan, F. M., Williams, R. O., Cope, A. P., Gibbons, D. L., Katsikis, P. D., and Maini, R. N. (1992) Evaluation of the role of cytokines in autoimmune disease: the importance of TNF alpha in rheumatoid arthritis. Prog. Growth Factor Res. 4, 247–55.

    Google Scholar 

  90. Tartaglia, L. A., Goeddel, D. V. (1992) Two T’NF receptors. Immunol. Today 13, 151–153.

    Article  PubMed  CAS  Google Scholar 

  91. Rothe, M., Wong, S. C., Henzel, W. J., and Goeddel, D. V. (1994) A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78, 681–692.

    Article  PubMed  CAS  Google Scholar 

  92. Hsu, H., Xiong, J., Goeddel, D. V. (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81, 495–504.

    Article  PubMed  CAS  Google Scholar 

  93. Hsu, H. L., Shu, H. B., Pan, M. G., and Goeddel, D. V. (1996) TRADDTRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299–308.

    Article  PubMed  CAS  Google Scholar 

  94. Decoster, E., Vanhaesebroeck, B., Vandenabeele, P., Grooten, J., and Fiers, W. (1995) Generation and biological characterization of membrane-bound, uncleavable murine tumor necrosis factor. J. Biol. Chem. 270, 18473–18478.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bluethmann, H. (1998). Physiological, Immunological, and Pathological Functions of Tumor Necrosis Factor (TNF) Revealed by TNF Receptor-Deficient Mice. In: Durum, S.K., Muegge, K. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2753-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2753-1_5

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-2755-5

  • Online ISBN: 978-1-4757-2753-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics