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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jun;87(12):4449–4452. doi: 10.1073/pnas.87.12.4449

Specific inhibition of interleukin 3 bioactivity by a monoclonal antibody reactive with hematopoietic progenitor cells.

P D Emanuel 1, S C Peiper 1, Z Chen 1, D C Sheng 1, K S Zuckerman 1
PMCID: PMC54132  PMID: 2352928

Abstract

HIM1, originally designated HI98, a murine monoclonal IgM antibody raised against human mononuclear cells, has been reported at the Fourth International Leukocyte Typing Workshop (called antibody M0141) to be the only one of 157 antibodies tested that inhibited binding of interleukin 3 (IL-3) to KG-1 human acute myelogenous leukemia cells and normal human monocytes. We have carried out detailed studies of the selective effect of HIM1 on IL-3-mediated stimulation of hematopoietic progenitors. Preincubation of normal human bone marrow mononuclear cells, depleted of adherent cells and T cells, with HIM1 antibody resulted in a dose-dependent inhibition of IL-3-mediated stimulation of both erythroid burst-forming units (maximum inhibition 55%) and granulocyte/macrophage colony-forming units (maximum inhibition 49%). HIM1 antibody had no effect on growth of erythroid colony-forming units in culture. In addition, preincubation of the cells with HIM1 antibody had no deleterious effect on granulocyte/macrophage colony-stimulating factor-induced growth of either erythroid bursts or granulocyte/macrophage colonies. To be certain that the HIM1 antibody did not react directly with IL-3 itself, we attempted to use immunodepletion to remove IL-3 that had been added to our culture medium. Although we were able to remove IL-3 bioactivity by immunodepletion with anti-IL-3 antibody bound to Sepharose beads, beads with attached HIM1 did not remove IL-3 activity from the medium. Polymorphonuclear neutrophils bind high levels of HIM1, although they have very few or no detectable IL-3 receptors. Therefore, this antibody appears to recognize a cell surface antigen that is critical for optimal IL-3 binding and bioactivity but is not the actual IL-3 receptor.

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Selected References

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

  1. Berdel W. E., Danhauser-Riedl S., Steinhauser G., Winton E. F. Various human hematopoietic growth factors (interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells. Blood. 1989 Jan;73(1):80–83. [PubMed] [Google Scholar]
  2. Bomsztyk K., Sims J. E., Stanton T. H., Slack J., McMahan C. J., Valentine M. A., Dower S. K. Evidence for different interleukin 1 receptors in murine B- and T-cell lines. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8034–8038. doi: 10.1073/pnas.86.20.8034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang J. M., Metcalf D., Lang R. A., Gonda T. J., Johnson G. R. Nonneoplastic hematopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL-3) expression. Blood. 1989 May 1;73(6):1487–1497. [PubMed] [Google Scholar]
  4. Chizzonite R., Truitt T., Kilian P. L., Stern A. S., Nunes P., Parker K. P., Kaffka K. L., Chua A. O., Lugg D. K., Gubler U. Two high-affinity interleukin 1 receptors represent separate gene products. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8029–8033. doi: 10.1073/pnas.86.20.8029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. D'Andrea A. D., Fasman G. D., Lodish H. F. Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family. Cell. 1989 Sep 22;58(6):1023–1024. doi: 10.1016/0092-8674(89)90499-6. [DOI] [PubMed] [Google Scholar]
  6. D'Andrea A. D., Lodish H. F., Wong G. G. Expression cloning of the murine erythropoietin receptor. Cell. 1989 Apr 21;57(2):277–285. doi: 10.1016/0092-8674(89)90965-3. [DOI] [PubMed] [Google Scholar]
  7. Delwel R., Dorssers L., Touw I., Wagemaker G., Löwenberg B. Human recombinant multilineage colony stimulating factor (interleukin-3): stimulator of acute myelocytic leukemia progenitor cells in vitro. Blood. 1987 Jul;70(1):333–336. [PubMed] [Google Scholar]
  8. Gearing D. P., King J. A., Gough N. M., Nicola N. A. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J. 1989 Dec 1;8(12):3667–3676. doi: 10.1002/j.1460-2075.1989.tb08541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gesner T. G., Mufson R. A., Norton C. R., Turner K. J., Yang Y. C., Clark S. C. Specific binding, internalization, and degradation of human recombinant interleukin-3 by cells of the acute myelogenous, leukemia line, KG-1. J Cell Physiol. 1988 Sep;136(3):493–499. doi: 10.1002/jcp.1041360314. [DOI] [PubMed] [Google Scholar]
  10. Gesner T., Mufson R. A., Turner K. J., Clark S. C. Identification through chemical cross-linking of distinct granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors on myeloid leukemic cells, KG-1. Blood. 1989 Dec;74(8):2652–2656. [PubMed] [Google Scholar]
  11. Hatakeyama M., Tsudo M., Minamoto S., Kono T., Doi T., Miyata T., Miyasaka M., Taniguchi T. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989 May 5;244(4904):551–556. doi: 10.1126/science.2785715. [DOI] [PubMed] [Google Scholar]
  12. Ihle J. N., Keller J., Oroszlan S., Henderson L. E., Copeland T. D., Fitch F., Prystowsky M. B., Goldwasser E., Schrader J. W., Palaszynski E. Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. J Immunol. 1983 Jul;131(1):282–287. [PubMed] [Google Scholar]
  13. Lopez A. F., Dyson P. G., To L. B., Elliott M. J., Milton S. E., Russell J. A., Juttner C. A., Yang Y. C., Clark S. C., Vadas M. A. Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series. Blood. 1988 Nov;72(5):1797–1804. [PubMed] [Google Scholar]
  14. Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
  15. Murthy S. C., Mui A. L., Krystal G. Characterization of the interleukin 3 receptor. Exp Hematol. 1990 Jan;18(1):11–17. [PubMed] [Google Scholar]
  16. Nicola N. A., Metcalf D. Binding of iodinated multipotential colony-stimulating factor (interleukin-3) to murine bone marrow cells. J Cell Physiol. 1986 Aug;128(2):180–188. doi: 10.1002/jcp.1041280207. [DOI] [PubMed] [Google Scholar]
  17. Otsuka T., Miyajima A., Brown N., Otsu K., Abrams J., Saeland S., Caux C., de Waal Malefijt R., de Vries J., Meyerson P. Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones. J Immunol. 1988 Apr 1;140(7):2288–2295. [PubMed] [Google Scholar]
  18. Sawyer S. T., Krantz S. B., Sawada K. Receptors for erythropoietin in mouse and human erythroid cells and placenta. Blood. 1989 Jul;74(1):103–109. [PubMed] [Google Scholar]
  19. Schrader J. W. The panspecific hemopoietin of activated T lymphocytes (interleukin-3). Annu Rev Immunol. 1986;4:205–230. doi: 10.1146/annurev.iy.04.040186.001225. [DOI] [PubMed] [Google Scholar]
  20. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  21. Taga T., Hibi M., Hirata Y., Yamasaki K., Yasukawa K., Matsuda T., Hirano T., Kishimoto T. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989 Aug 11;58(3):573–581. doi: 10.1016/0092-8674(89)90438-8. [DOI] [PubMed] [Google Scholar]
  22. Yamasaki K., Taga T., Hirata Y., Yawata H., Kawanishi Y., Seed B., Taniguchi T., Hirano T., Kishimoto T. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988 Aug 12;241(4867):825–828. doi: 10.1126/science.3136546. [DOI] [PubMed] [Google Scholar]
  23. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
  24. Ymer S., Tucker W. Q., Sanderson C. J., Hapel A. J., Campbell H. D., Young I. G. Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene. Nature. 1985 Sep 19;317(6034):255–258. doi: 10.1038/317255a0. [DOI] [PubMed] [Google Scholar]
  25. Zuckerman K. S., Bagby G. C., Jr, McCall E., Sparks B., Wells J., Patel V., Goodrum D. A monokine stimulates production of human erythroid burst-promoting activity by endothelial cells in vitro. J Clin Invest. 1985 Feb;75(2):722–725. doi: 10.1172/JCI111752. [DOI] [PMC free article] [PubMed] [Google Scholar]

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