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Lymphotoxins, a Multicomponent Family of Effector Molecules

Purification of Human α-Lymphotoxin from a Cloned Continuous Lymphoblastoid Cell Line IR 3.4 to Homogeneity
  • Gale A. Granger
  • Diane L. Johnson
  • J. Michael Plunkett
  • Irene K. Masunaka
  • Sally L. Orr
  • Robert S. Yamamoto
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Human lymphotoxins (LT) are a multicomponent family of related and distinct cell-lytic and growth inhibitory glycoproteins (Toth and Granger, 1979). They are inducible and can be released specifically when immune lymphoid cells are cocul-tured with the immunizing antigen or nonspecifically when nonimmune lymphoid cells are cocultured with lectins (Daynes and Granger, 1974; Granger and Williams, 1968; Granger et al., 1969). An exception to the inducible mode of release of these effector molecules is that certain continuous human lymphoblastoid cell lines con-stitutively release low levels of LT in vitro (Fair et al., 1979; Granger et al., 1970; Khan et al., 1982). There is now evidence that certain LT forms may have a role as lytic effectors in different classes of cell destructive reactions mediated by human lymphocytes in vitro (Weitzen et al., 1983a,b; Yamamoto et al., 1979, 1984b). However, the situation is complex for it is clear that different classes of effector lymphocytes (T cells, NK cells) can release different LT forms (Harris et al., 1981; Weitzen et al., 1983a,b; Wright and Bonavida, 1982; Yamamoto et al., 1984a). Moreover, in these reactions the different LT forms may assemble together to induce cell lysis as molecular complexes or alternatively may act as individual components on a target cell in a synergistic fashion.

Keywords

Phorbol Myristate Acetate Lytic Activity Phorbol Myristate Acetate Roller Bottle DEAE Column 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aggarwal, B., Moffat, B., and Harkins, R. N., 1982, Purification and characterization of lymphotoxin from human lymphoblastoid cell line 1788, Third International Lymphokine Workshop, Haverford, Pennsylvania.Google Scholar
  2. Davis, B., 1964, Disc electrophoresis. II. Methods and application to human serum proteins, Ann. N.Y. Acad. Sci. 121:404.PubMedCrossRefGoogle Scholar
  3. Daynes, R. A., and Granger, G. A., 1974, The regulation of lymphotoxin release from stimulated human lymphocyte cultures: The requirement for continual mitogen stimulation, Cell. Immunol. 12:252.PubMedCrossRefGoogle Scholar
  4. Devlin, J. J., Yamamoto, R. S., and Granger, G. A., 1981, Stabilization and functional studies of high molecular weight murine lymphotoxins, Cell. Immunol. 61:22.PubMedCrossRefGoogle Scholar
  5. Devlin, J. J., Klostergaard, J., and Granger, G. A., 1983, J. Immunol., submitted.Google Scholar
  6. Fair, D. S., Jeffes, E. W. B., and Granger, G. A., 1979, Release of LT molecules with restricted physical heterogeneity by a continuous human lymphoid cell line in vitro, Mol. Immunol. 16: 186.CrossRefGoogle Scholar
  7. Furlong, C. E., Cirakoglu, C., Willis, R. C., and Santy, P. A., 1973, A simple preparative Polyacrylamide disc gel electrophoresis apparatus: Purification of three branched-chain amino acid binding proteins from E. coli, Anal. Biochem. 15:297.CrossRefGoogle Scholar
  8. Granger, G. A., and Williams, T. W., 1968, Lymphocyte cytotoxicity in vitro: Activation and release of a cytotoxic factor, Nature (London) 218:1253.CrossRefGoogle Scholar
  9. Granger, G. A., Shacks, S. J., Williams, T. W., and Kolb, W. P., 1969, Lymphocyte in vitro cytotoxicity: Specific release of lymphotoxin-like materials from tuberculin sensitive lymphocyte cells, Nature (London) 221:1155.CrossRefGoogle Scholar
  10. Granger, G. A., Moore, G. E., White, J. G., Matzinger, P., Sundsomo, J. S., Shupe, S., Kolb, W. P., Kramer, J., and Glade, P. R., 1970, Production of lymphotoxin and migration inhibitory factor by established human lymphocytic cell lines, J. Immunol. 104:1476.PubMedGoogle Scholar
  11. Granger, G. A., Yamamoto, R. S., Fair, D. S., and Hiserodt, J. C., 1978, The human LT system. I. Physical-chemical heterogeneity of LT molecules released by mitogen activated human lymphocytes in vitro, Cell. Immunol. 38:388.CrossRefGoogle Scholar
  12. Granger, G. A., Yamamoto, R. S., Ware, C. F., and Ross, M. W., 1980, In vitro detection of human lymphotoxin, in: Manual of Clinical Immunology (N. R. Rose and H. Friedman, eds.), American Society for Microbiology, Washington, D. C.Google Scholar
  13. Harris, P. C., Yamamoto, R. S., Crane, J., and Granger, G. A., 1981, The human LT system. X. The first cell-lytic molecule released by enriched lymphocytes is a 150,000 MW form in association with small non-lytic components, J. Immunol. 126:2165.PubMedGoogle Scholar
  14. Hiserodt, J. C., Fair, D. S., and Granger, G. A., 1976, Identification of multiple cytolytic components associated with the β-LT class of lymphotoxins released by mitogen activated human lymphocytes in vitro, J. Immunol. 117:1503.Google Scholar
  15. Khan, A., Weldon, D., Duvall, J., Pichyangkul, S., Hill, N. O., Muntz, D., Lanius, R., and Ground, M., 1982, A standardized automated computer assisted micro-assay for lymphotoxin, in: Human Lymphokines: The Biological Immune Response Modifiers (A. Khan and N. O. Hill, eds.), Academic Press, New York.Google Scholar
  16. Klostergaard, J., Long, S., and Granger, G. A., 1981a, Purification of human a class lymphotoxin to electrophoretic homogeneity, Mol. Immunol. 18:1049.CrossRefGoogle Scholar
  17. Klostergaard, J., Yamamoto, R. S., and Granger, G. A., 1981b, Lymphotoxins: Purification and biological parameters, in: Lymphokines and Thymic Factors and Their Potential Utilization in Cancer Therapeutics (A. L. Goldstein, ed.), Raven Press, New York.Google Scholar
  18. Klostergaard, J., Yamamoto, R. S., Harris, P. C., and Granger, G. A., 1981c, The nature of a lymphocyte released cell toxin, in: Handbook of Cancer Immunology (H. Water, ed.), Garland STPM Press, New York.Google Scholar
  19. Kramer, J. J., and Granger, G. A., 1972, An improved in vitro assay for lymphotoxin, Cell. Immunol. 3:144–149.PubMedCrossRefGoogle Scholar
  20. Lee, S. C., and Lucas, Z. J., 1976, Regulatory factors produced by lymphocytes. I. The occurrence of multiple α-lymphotoxins associated with ribonuclease activity, J. Immunol. 117:283.PubMedGoogle Scholar
  21. Lisafeld, B. A., Minowada, J., Klein, E., and Holterman, O. A., 1980, Lymphotoxins: Selective cytotoxic effects, Int. Archs. Allergy Appl. Immunol. 62:59.CrossRefGoogle Scholar
  22. O’Farrell, P. D., 1975, High resolution two-dimensional electrophoresis of proteins, J. Biol. Chem. 250:4007.PubMedGoogle Scholar
  23. Ross, M. W., Tiangco, G. J., Horn, P., Hiserodt, J. C., and Granger, G. A., 1979, The LT system in experimental animals. III. Physical-chemical characteristics and relationships of lymphotoxin (LT) molecules released in vitro, J. Immunol. 123:325.PubMedGoogle Scholar
  24. Toth, M. K., and Granger, G. A., 1979, The human LT system. VI. Identification of various saccharides on LT molecules and their contribution to cytotoxicity and charge heterogeneity, Mol. Immunol. 16:671.PubMedCrossRefGoogle Scholar
  25. Weitzen, M. L., Innins, E., Yamamoto, R. S., and Granger, G. A., 1983a, Inhibition of human NK induced cell lysis and soluble cell-lytic molecules with anti-human LT antisera and various saccharides, Cell. Immunol. 77: 42. CrossRefGoogle Scholar
  26. Weitzen, M. L., Yamamoto, R. S., and Granger, G. A., 1983b, Identification of lymphocyte-derived lymphotoxins with binding and cell-lytic activity on NK sensitive cell lines in vitro, Cell. Immunol. 77:30.CrossRefGoogle Scholar
  27. Williams, T. W., and Bellanti, J. A., 1983, In vitro synergism between interferons and human lymphotoxins: Enhancement of lymphotoxin-induced target cell killing, J. Immunol. 130:518.PubMedGoogle Scholar
  28. Williams, T. W., and Granger, G. A., 1969, Lymphocyte in vitro cytotoxicity: Mechanism of lymphotoxin induced cell destruction, J. Immunol. 102:911.PubMedGoogle Scholar
  29. Wright, S. C., and Bonavida, B., 1982, Selective lysis of NK-sensitive target cells by a soluble mediator released from murine spleen cells and human peripheral blood lymphocytes, J. Immunol. 126:1516.Google Scholar
  30. Yamamoto, R. S., Hiserodt, J. C., Lewis, J. E., Carmack, C. E., and Granger, G. A., 1978, The human LT system. II. Immunological relationships of LT molecules released by mitogen activated human lymphocytes in vitro, Cell. Immunol. 38:403.CrossRefGoogle Scholar
  31. Yamamoto, R. S., Hiserodt, J. C., and Granger, G. A., 1979, The human LT system. V. A comparison of the relative lytic effectiveness of various MW human LT classes on 51Cr labeled allogeneic target cells in vitro, Cell. Immunol. 45:261.CrossRefGoogle Scholar
  32. Yamamoto, R. S., Johnson, D. L., Masunaka, I. K., and Granger, G. A., 1984a, Phorbal myristate acetate induction of lymphotoxins from continuous human B lymphoid cell lines in vitro, J. Biol. Response Modifiers, 3:76.Google Scholar
  33. Yamamoto, R. S., Ware, C. F., and Granger, G. A., 1984b, in preparation.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Gale A. Granger
    • 1
  • Diane L. Johnson
    • 1
  • J. Michael Plunkett
    • 1
  • Irene K. Masunaka
    • 1
  • Sally L. Orr
    • 1
  • Robert S. Yamamoto
    • 1
  1. 1.Department of Molecular Biology and BiochemistryUniversity of CaliforniaIrvineUSA

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