Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Jun;92(3):537–542. doi: 10.1111/j.1365-2249.1993.tb03434.x

A soluble form of the human transferrin receptor is released by activated lymphocytes in vitro.

W Woith 1, I Nüsslein 1, C Antoni 1, D I Dejica 1, T H Winkler 1, M Herrmann 1, K Pirner 1, J R Kalden 1, B Manger 1
PMCID: PMC1554787  PMID: 8513587

Abstract

Soluble transferrin receptors (sTfR) were detected in culture supernatants of activated human peripheral blood mononuclear cells (PBMC) using a sandwich ELISA technique with two non-cross-reacting TfR MoAbs. Mitogenic stimulation of lymphoid cells induced both up-regulation of TfR surface density and release of sTfR to the medium. Peak levels of sTfR in culture supernatants occurred at day 4 after activation, 1 day later than maximum expression of TfR in the plasma membrane. Production of sTfR was independent of proliferation, as demonstrated by measuring sTfR release by PBMC, which had been irradiated with a dose of 20 Gy before activation. In addition to these in vitro experiments, we tested the sera of 85 patients with systemic lupus erythematosus (SLE), an autoimmune disease accompanied by in vivo activation of lymphocytes, for their sTfR levels. No correlation of these data was detectable to serum concentrations of the soluble alpha-chain of the IL-2 receptor, an unequivocal marker of lymphocyte activation. However, they correlated negatively to the haemoglobin content of the patients' erythrocytes, indicating that erythroid progenitors are the predominant source of sTfR in SLE patients' sera.

Full text

PDF
537

Selected References

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

  1. Beguin Y., Huebers H. A., Josephson B., Finch C. A. Transferrin receptors in rat plasma. Proc Natl Acad Sci U S A. 1988 Jan;85(2):637–640. doi: 10.1073/pnas.85.2.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chitambar C. R., Loebel A. L., Noble N. A. Shedding of transferrin receptor from rat reticulocytes during maturation in vitro: soluble transferrin receptor is derived from receptor shed in vesicles. Blood. 1991 Nov 1;78(9):2444–2450. [PubMed] [Google Scholar]
  3. Chitambar C. R., Zivkovic-Gilgenbach Z. Influence of cellular iron status on the release of soluble transferrin receptor from human promyelocytic leukemic HL60 cells. J Lab Clin Med. 1990 Sep;116(3):345–353. [PubMed] [Google Scholar]
  4. Chitambar C. R., Zivkovic Z. Release of soluble transferrin receptor from the surface of human leukemic HL60 cells. Blood. 1989 Aug 1;74(2):602–608. [PubMed] [Google Scholar]
  5. Cook J. D., Skikne B. S. Iron deficiency: definition and diagnosis. J Intern Med. 1989 Nov;226(5):349–355. doi: 10.1111/j.1365-2796.1989.tb01408.x. [DOI] [PubMed] [Google Scholar]
  6. Dautry-Varsat A., Ciechanover A., Lodish H. F. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2258–2262. doi: 10.1073/pnas.80.8.2258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferguson B. J., Skikne B. S., Simpson K. M., Baynes R. D., Cook J. D. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab Clin Med. 1992 Apr;119(4):385–390. [PubMed] [Google Scholar]
  8. Flowers C. H., Skikne B. S., Covell A. M., Cook J. D. The clinical measurement of serum transferrin receptor. J Lab Clin Med. 1989 Oct;114(4):368–377. [PubMed] [Google Scholar]
  9. Guesdon J. L., Ternynck T., Avrameas S. The use of avidin-biotin interaction in immunoenzymatic techniques. J Histochem Cytochem. 1979 Aug;27(8):1131–1139. doi: 10.1177/27.8.90074. [DOI] [PubMed] [Google Scholar]
  10. Huebers H. A., Beguin Y., Pootrakul P., Einspahr D., Finch C. A. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood. 1990 Jan 1;75(1):102–107. [PubMed] [Google Scholar]
  11. Johnstone R. M., Bianchini A., Teng K. Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions. Blood. 1989 Oct;74(5):1844–1851. [PubMed] [Google Scholar]
  12. Kohgo Y., Niitsu Y., Kondo H., Kato J., Tsushima N., Sasaki K., Hirayama M., Numata T., Nishisato T., Urushizaki I. Serum transferrin receptor as a new index of erythropoiesis. Blood. 1987 Dec;70(6):1955–1958. [PubMed] [Google Scholar]
  13. Kohgo Y., Nishisato T., Kondo H., Tsushima N., Niitsu Y., Urushizaki I. Circulating transferrin receptor in human serum. Br J Haematol. 1986 Oct;64(2):277–281. doi: 10.1111/j.1365-2141.1986.tb04120.x. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Manger B., Weiss A., Hardy K. J., Stobo J. D. A transferrin receptor antibody represents one signal for the induction of IL 2 production by a human T cell line. J Immunol. 1986 Jan;136(2):532–538. [PubMed] [Google Scholar]
  16. Müllner E. W., Kühn L. C. A stem-loop in the 3' untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm. Cell. 1988 Jun 3;53(5):815–825. doi: 10.1016/0092-8674(88)90098-0. [DOI] [PubMed] [Google Scholar]
  17. Nair M. K., Ebner K. E., Cook J. D. Isolation and characterization of a transferrin binding protein from rat plasma. Biochim Biophys Acta. 1990 Sep 14;1035(3):306–312. doi: 10.1016/0304-4165(90)90093-c. [DOI] [PubMed] [Google Scholar]
  18. Neckers L. M., Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3494–3498. doi: 10.1073/pnas.80.11.3494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pan B. T., Johnstone R. M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983 Jul;33(3):967–978. doi: 10.1016/0092-8674(83)90040-5. [DOI] [PubMed] [Google Scholar]
  20. Rubin L. A., Kurman C. C., Fritz M. E., Biddison W. E., Boutin B., Yarchoan R., Nelson D. L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed] [Google Scholar]
  21. Schneider C., Sutherland R., Newman R., Greaves M. Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9. J Biol Chem. 1982 Jul 25;257(14):8516–8522. [PubMed] [Google Scholar]
  22. Shih Y. J., Baynes R. D., Hudson B. G., Flowers C. H., Skikne B. S., Cook J. D. Serum transferrin receptor is a truncated form of tissue receptor. J Biol Chem. 1990 Nov 5;265(31):19077–19081. [PubMed] [Google Scholar]
  23. Skikne B. S., Flowers C. H., Cook J. D. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood. 1990 May 1;75(9):1870–1876. [PubMed] [Google Scholar]
  24. Sutherland R., Delia D., Schneider C., Newman R., Kemshead J., Greaves M. Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515–4519. doi: 10.1073/pnas.78.7.4515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  26. Trowbridge I. S. Immunoassay of serum transferrin receptors: clinical implications. J Lab Clin Med. 1989 Oct;114(4):336–337. [PubMed] [Google Scholar]
  27. Turkewitz A. P., Amatruda J. F., Borhani D., Harrison S. C., Schwartz A. L. A high yield purification of the human transferrin receptor and properties of its major extracellular fragment. J Biol Chem. 1988 Jun 15;263(17):8318–8325. [PubMed] [Google Scholar]
  28. Valentijn R. M., van Overhagen H., Hazevoet H. M., Hermans J., Cats A., Daha M. R., van ES L. A. The value of complement and immune complex determinations in monitoring disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 1985 Aug;28(8):904–913. doi: 10.1002/art.1780280810. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES