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. 1988 May;64(1):73–79.

Role of a SER immune suppressor in immune surveillance.

S K Oh 1, S Ross 1, J Walker 1, S Zeisel 1
PMCID: PMC1385188  PMID: 3260218

Abstract

A potent immunosuppressor factor, known as SER (suppressive E-receptor factor) has been identified in the body fluids of cancer patients. SER has been proven to be immunochemically analogous to the fetal form of haptoglobin. In this paper, we examine the role of SER immune suppressor in the immune surveillance mechanism of the host, using an affinity-purified SER. As shown in this study, SER, at microgram/ml concentrations, inhibits the T-cell proliferation induced with either monoclonal or polyclonal T-cell activators in vitro in human, and also inhibits the primary antibody response to T-dependent antigens in vivo in mice. Likewise, SER also inhibits the immunoglobulin synthesis of human B lymphocytes induced by a B-cell mitogen, pokeweed mitogen, in the presence of a tumour promoter, phorbol myristate acetate (PMA). In contrast to the T-dependent antibody response in vivo in mice or T-dependent mitogen response in vitro in human, SER does not interfere with the T-independent antibody responses to DNP-Ficoll or TNP-LPS in mice. SER also interferes with the natural killer cell function of human peripheral blood mononuclear cells. Although SER inhibits the phagocytic functions of human peripheral neutrophils, it requires at least 10-20 times the concentration of SER present in normal human plasma. Since this concentration of SER is attainable in the sera of solid tumour-bearing patients, highly elevated levels of SER could predispose the patients to microbial infections as well. This study demonstrates that purified SER manifests multi-faceted down-regulatory effects on the defence mechanism of hosts, thereby it could compromise the patients' cell-mediated immunity in vivo.

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Selected References

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  1. Badger A. M., Cooperband S. R., Merluzzi V. J., Glasgow A. H. Immunosuppressive activity of ascitic fluid from patients with cancer metastatic to the peritoneum. Cancer Res. 1977 Apr;37(4):1220–1226. [PubMed] [Google Scholar]
  2. Badger A. M., Oh S. K., Moolten F. R. Differential effects of an immunosuppressive fraction from ascites fluid of patients with ovarian cancer on spontaneous and antibody-dependent cytotoxicity. Cancer Res. 1981 Mar;41(3):1133–1139. [PubMed] [Google Scholar]
  3. Baseler M. W., Burrell R. Purification of haptoglobin and its effects on lymphocyte and alveolar macrophage responses. Inflammation. 1983 Dec;7(4):387–400. doi: 10.1007/BF00916303. [DOI] [PubMed] [Google Scholar]
  4. Bennett M., Schmid K. Immunosuppression by human plasma alpha 1-acid glycoprotein: importance of the carbohydrate moiety. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6109–6113. doi: 10.1073/pnas.77.10.6109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boyum A. Separation of blood leucocytes, granulocytes and lymphocytes. Tissue Antigens. 1974;4(4):269–274. [PubMed] [Google Scholar]
  6. Breit S. N., Wakefield D., Robinson J. P., Luckhurst E., Clark P., Penny R. The role of alpha 1-antitrypsin deficiency in the pathogenesis of immune disorders. Clin Immunol Immunopathol. 1985 Jun;35(3):363–380. doi: 10.1016/0090-1229(85)90097-2. [DOI] [PubMed] [Google Scholar]
  7. Burstein M., Scholnick H. R., Morfin R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res. 1970 Nov;11(6):583–595. [PubMed] [Google Scholar]
  8. Ceuppens J. L., Goodwin J. S. Regulation of immunoglobulin production in pokeweed mitogen-stimulated cultures of lymphocytes from young and old adults. J Immunol. 1982 Jun;128(6):2429–2434. [PubMed] [Google Scholar]
  9. Cooperband S. R., Bondevik H., Schmid K., Mannick J. A. Transformation of human lymphocytes: inhibition by homologous alpha globulin. Science. 1968 Mar 15;159(3820):1243–1244. doi: 10.1126/science.159.3820.1243. [DOI] [PubMed] [Google Scholar]
  10. Gavison-Goren R., Nelken D. Non-specific normal immunosuppressive protein (Nip): purification and further biochemical characterization. Immunology. 1983 Aug;49(4):599–608. [PMC free article] [PubMed] [Google Scholar]
  11. Glaser M., Ofek I., Nelken D. Inhibition of plaque formation, rosette formation and phagocytosis by alpha globulin. Immunology. 1972 Aug;23(2):205–214. [PMC free article] [PubMed] [Google Scholar]
  12. Glaser M., Ting C. C., Herberman R. B. In vitro inhibition of cell-mediated cytotoxicity against syngeneic Friend virus-induced leukemia by immunoregulatory alpha globulin. J Natl Cancer Inst. 1975 Dec;55(6):1477–1479. doi: 10.1093/jnci/55.6.1477. [DOI] [PubMed] [Google Scholar]
  13. Glasgow A. H., Nimberg R. B., Menzoian J. O., Saporoschetz I., Cooperband S. R., Schmid K., Mannick J. A. Association of anergy with an immunosuppressive peptide fraction in the serum of patients with cancer. N Engl J Med. 1974 Dec 12;291(24):1263–1267. doi: 10.1056/NEJM197412122912401. [DOI] [PubMed] [Google Scholar]
  14. Goren R., Nelken D. The inhibitory effect of normal immunosuppressive protein on lymphocytes mediating natural killing activity. Immunology. 1981 Mar;42(3):427–430. [PMC free article] [PubMed] [Google Scholar]
  15. Hess A. D., Gall S. A., Dawson J. R. Inhibition of human lymphoblastoid cell line proliferation by ascites fluids from ovarian cancer patients. Cancer Res. 1980 Dec;40(12):4495–4500. [PubMed] [Google Scholar]
  16. Jacobs M. D., Morrison D. C. Dissociation between mitogenicity and immunogenicity of TNP-lipopolysaccharide, a T-independent antigen. J Exp Med. 1975 Jun 1;141(6):1453–1458. doi: 10.1084/jem.141.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KAMRIN B. B. Successful skin bomografts in mature non-littermate rats treated with fractions containing alpha-globulins. Proc Soc Exp Biol Med. 1959 Jan;100(1):58–61. doi: 10.3181/00379727-100-24522. [DOI] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. McMaster P. R., Bachvaroff R. J., Rapaport F. T. Mechanisms of antibody formation. II. Use of DNP-Ficoll in studies of hapten-specific B-cell responses. Cell Immunol. 1975 Nov;20(1):42–53. doi: 10.1016/0008-8749(75)90082-9. [DOI] [PubMed] [Google Scholar]
  20. Menzoian J. O., Glasgow A. H., Nimberg R. D., Cooperband S. R., Schmid K., Saporoschetz I., Mannick J. A. Regulation of T lymphocyte function by immunoregulatory alphaglobulin (IRA). J Immunol. 1974 Jul;113(1):266–273. [PubMed] [Google Scholar]
  21. Morgan A. C., Jr, McIntyre R. F. Monoclonal antibodies to human melanoma-associated antigens: an amplified enzyme-linked immunosorbent assay for the detection of antigen, antibody, and immune complexes. Cancer Res. 1983 Jul;43(7):3155–3159. [PubMed] [Google Scholar]
  22. Nelken D., Ovadia H., Hanna N. Normal immunosuppressive protein inhibition of human and murine lymphoblastoid cell line proliferation. Eur J Immunol. 1979 Feb;9(2):176–177. doi: 10.1002/eji.1830090216. [DOI] [PubMed] [Google Scholar]
  23. Occhino J. C., Glasgow A. H., Cooperband S. R., Mannick J. A., Schmid K. Isolation of an immunosuppressive peptide fraction from human plasma. J Immunol. 1973 Mar;110(3):685–694. [PubMed] [Google Scholar]
  24. Oh S. K., Lapenson D. P. E receptor-related immunosuppressive factor in malignant pleural fluid and plasma: molecular mechanism of action on DNA-polymerase-alpha. J Immunol. 1985 Jul;135(1):355–361. [PubMed] [Google Scholar]
  25. Oh S. K., Leung M. F., Knee T., Williams J. M. Biological properties of suppressive E-receptor factor on lymphokine function. Eur J Immunol. 1987 Oct;17(10):1403–1409. doi: 10.1002/eji.1830171003. [DOI] [PubMed] [Google Scholar]
  26. Oh S. K., Moolten F. L. Nonspecific immunosuppressive factors in malignant ascites: further characterization and possible relationship to erythrocyte receptors of human peripheral T cells. J Immunol. 1981 Dec;127(6):2300–2307. [PubMed] [Google Scholar]
  27. Oh S. K., Moolten F. L. Purification and characterization of an immunosuppressive factor from ovarian cancer ascites fluid. Eur J Immunol. 1981 Oct;11(10):780–788. doi: 10.1002/eji.1830111009. [DOI] [PubMed] [Google Scholar]
  28. Oh S. K., Sipe J. D., Skinner M., Sullivan R. Quantitation of serum suppressor factor, related to the erythrocyte receptor of human peripheral blood T lymphocytes as measured by radioimmunoassay. Clin Immunol Immunopathol. 1984 Jun;31(3):430–438. doi: 10.1016/0090-1229(84)90095-3. [DOI] [PubMed] [Google Scholar]
  29. Oh S. K., Very D. L., Walker J., Raam S., Ju S. T. An analogy between fetal haptoglobin and a potent immunosuppressant in cancer. Cancer Res. 1987 Oct 1;47(19):5120–5126. [PubMed] [Google Scholar]
  30. Rademacher B. E., Steele W. J. A general method for the isolation of haptoglobin 1-1, 2-1, and 2-2 from human plasma. Anal Biochem. 1987 Jan;160(1):119–126. doi: 10.1016/0003-2697(87)90621-x. [DOI] [PubMed] [Google Scholar]
  31. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  32. Volanakis J. E. Complement activation by C-reactive protein complexes. Ann N Y Acad Sci. 1982;389:235–250. doi: 10.1111/j.1749-6632.1982.tb22140.x. [DOI] [PubMed] [Google Scholar]
  33. Waldmann T. A., Broder S. Polyclonal B-cell activators in the study of the regulation of immunoglobulin synthesis in the human system. Adv Immunol. 1982;32:1–63. doi: 10.1016/s0065-2776(08)60720-8. [DOI] [PubMed] [Google Scholar]
  34. Wang B. S., Badger A. M., Nimberg R. R., Cooperband S. R., Schmid K., Mannick J. A. Suppression of tumor-specific cell-mediated cytotoxicity by immunoregulatory alpha-globulin and by immunoregulatory alpha-globulin-like peptides from cancer patients. Cancer Res. 1977 Sep;37(9):3022–3025. [PubMed] [Google Scholar]
  35. Weigle W. O., Morgan E. L., Goodman M. G., Chenoweth D. E., Hugli T. E. Modulation of the immune response by anaphylatoxin in the microenvironment of the interacting cells. Fed Proc. 1982 Dec;41(14):3099–3103. [PubMed] [Google Scholar]
  36. Yamamura M., Boler J., Valdimarsson H. Phagocytosis measured as inhibition of uridine uptake by Candida albicans. J Immunol Methods. 1977;14(1):19–24. doi: 10.1016/s0022-1759(97)90016-8. [DOI] [PubMed] [Google Scholar]

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