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. 1980 Oct;77(10):6109–6113. doi: 10.1073/pnas.77.10.6109

Immunosuppression by human plasma alpha 1-acid glycoprotein: importance of the carbohydrate moiety.

M Bennett, K Schmid
PMCID: PMC350223  PMID: 6934536

Abstract

Human plasma alpha 1-acid glycoprotein (orosomucoid) and derivatives of this protein produced by sequential enzymatic cleavage of the glycosidic residue (sialic acid, galactose, N-acetylglucosamine, mannose) were tested for the ability suppress a number of immune functions of mouse spleen cells in vitro at physiological concentrations. alpha 1-Acid glycoprotein and especially the agalacto/asialo derivative suppressed (i) the mitogenic responses to concanavalin A, lipopolysaccharide, and alloantigens, (ii) antibody responses to sheep erythrocytes, and (iii) induction of cell-mediated lympholysis against allogeneic target cells. The native protein and its derivative did not inhibit the proliferation of EL-4 lymphoma cells and did not suppress the lysis of YAC-1 lymphoma cells by natural killer cells. The enhanced potency of the agalacto/asialo derivative indicates that the nature of the carbohydrate moiety exposed on the protein determines the effectiveness of the glycoprotein and its deglycosylated derivatives may function to regulate immune responses in various physiological and pathological conditions.

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Selected References

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

  1. Apffel C. A., Peters J. H. Tumors and serum glycoproteins. The 'symbodies'. Prog Exp Tumor Res. 1969;12:1–54. [PubMed] [Google Scholar]
  2. BURGI W., SCHMID K. Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma. J Biol Chem. 1961 Apr;236:1066–1074. [PubMed] [Google Scholar]
  3. Bacchus H. Serum glycoproteins and malignant neoplastic disorders. CRC Crit Rev Clin Lab Sci. 1977 Dec;8(4):333–362. doi: 10.3109/10408367709150913. [DOI] [PubMed] [Google Scholar]
  4. Berger E. G., Alpert E., Schmid K., Isselbacher K. J. Immunohistochemical localization of alpha1-acid-glycoprotein in human liver parenchymal cells. Histochemistry. 1977 Apr 4;51(4):293–296. doi: 10.1007/BF00494364. [DOI] [PubMed] [Google Scholar]
  5. Chapuis B., Brunner K. T. Cell mediated immune reactions "in vitro". Reactivity of lymphocytes from animals sensitized to chicken erythrocytes, tuberculin or transplantation antigens. Int Arch Allergy Appl Immunol. 1971;40(3):321–339. [PubMed] [Google Scholar]
  6. Chiu K. M., Mortensen R. F., Osmand A. P., Gewurz H. Interactions of alpha1-acid glycoprotein with the immune system. I. Purification and effects upon lymphocyte responsiveness. Immunology. 1977 Jun;32(6):997–1005. [PMC free article] [PubMed] [Google Scholar]
  7. Distler J. J., Jourdian G. W. The purification and properties of beta-galactosidase from bovine testes. J Biol Chem. 1973 Oct 10;248(19):6772–6780. [PubMed] [Google Scholar]
  8. Gahmberg C. G., Andersson L. C. Leukocyte surface origin of human alpha1-acid glycoprotein (orosomucoid). J Exp Med. 1978 Aug 1;148(2):507–521. doi: 10.1084/jem.148.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hymes A. J., Mullinax G. L., Mullinax F. Immunoglobulin carbohydrate requirement for formation of an IgG-IgG complex. J Biol Chem. 1979 May 10;254(9):3148–3151. [PubMed] [Google Scholar]
  10. Ip C., Dao T. L. Increase in serum and tissue glycosyltransferases and glycosidases in tumor-bearing rats. Cancer Res. 1977 Sep;37(9):3442–3447. [PubMed] [Google Scholar]
  11. Kumar V., Bennett M. Mechanisms of genetic resistance to Friend virus leukemia in mice. II. Resistance of mitogen-responsive lymphocytes mediated by marrow-dependent cells. J Exp Med. 1976 Apr 1;143(4):713–727. doi: 10.1084/jem.143.4.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kumar V., Luevano E., Bennett M. Hybrid resistance to EL-4 lymphoma cells. I. Characterization of natural killer cells that lyse EL-4 cells and their distinction from marrow-dependent natural killer cells. J Exp Med. 1979 Sep 19;150(3):531–547. doi: 10.1084/jem.150.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Merluzzi V. J., Levy E. M., Kumar V., Bennett M., Cooperband S. R. In vitro activation of suppressor cells from spleens of mice treated with radioactive strontium. J Immunol. 1978 Aug;121(2):505–512. [PubMed] [Google Scholar]
  15. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morell A. G., Gregoriadis G., Scheinberg I. H., Hickman J., Ashwell G. The role of sialic acid in determining the survival of glycoproteins in the circulation. J Biol Chem. 1971 Mar 10;246(5):1461–1467. [PubMed] [Google Scholar]
  17. Mortensen R. F., Osmand A. P., Gewurz H. Effects on C-reactive protein on the lymphoid system. I. Binding to thymus-dependent lymphocytes and alteration of their functions. J Exp Med. 1975 Apr 1;141(4):821–839. [PMC free article] [PubMed] [Google Scholar]
  18. Murgita R. A., Tomasi T. B., Jr Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response. J Exp Med. 1975 Feb 1;141(2):269–286. doi: 10.1084/jem.141.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Noonan F. P., Halliday W. J., Morton H., Clunie G. J. Early pregnancy factor is immunosuppressive. Nature. 1979 Apr 12;278(5705):649–651. doi: 10.1038/278649a0. [DOI] [PubMed] [Google Scholar]
  20. Prieels J. P., Pizzo S. V., Glasgow L. R., Paulson J. C., Hill R. L. Hepatic receptor that specifically binds oligosaccharides containing fucosyl alpha1 leads to 3 N-acetylglucosamine linkages. Proc Natl Acad Sci U S A. 1978 May;75(5):2215–2219. doi: 10.1073/pnas.75.5.2215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schachter H., Jabbal I., Hudgin R. L., Pinteric L., McGuire E. J., Roseman S. Intracellular localization of liver sugar nucleotide glycoprotein glycosyltransferases in a Golgi-rich fraction. J Biol Chem. 1970 Mar 10;245(5):1090–1100. [PubMed] [Google Scholar]
  22. Schmid K., Emura J., Schmid M. F., Stevens R. L., Nimberg R. B. Sequence comparison of human plasma alpha1-acid glycoprotein and the immunoglobulins. Int J Pept Protein Res. 1978 Jan;11(1):42–48. doi: 10.1111/j.1399-3011.1978.tb02819.x. [DOI] [PubMed] [Google Scholar]
  23. Shibata K., Okubo H., Ishibashi H., Tsuda-Kawamura K., Yanase T. Rat alpha 1-acid glycoprotein: uptake by inflammatory and tumour tissues. Br J Exp Pathol. 1978 Dec;59(6):601–608. [PMC free article] [PubMed] [Google Scholar]
  24. Tripodi D., Weis J. W., Bonness P. E., Pollack W. Identification of platelet orosomucoid. Transfusion. 1971 May-Jun;11(3):139–144. doi: 10.1111/j.1537-2995.1971.tb04391.x. [DOI] [PubMed] [Google Scholar]
  25. van Oss C. J., Gillman C. F., Bronson P. M., Border J. R. Phagocytosis-inhibiting properties of human serum alpha-1 acid glycoprotein. Immunol Commun. 1974;3(4):321–328. doi: 10.3109/08820137409061112. [DOI] [PubMed] [Google Scholar]

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