Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Jan 1;167(1):43–56. doi: 10.1084/jem.167.1.43

Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors

PMCID: PMC2188821  PMID: 3257253

Abstract

Using a clonal culture system, we investigated the hemopoietic effects of purified recombinant IL-5 obtained from conditioned media of transfected Xenopus oocytes. IL-5 alone acted on untreated bone marrow cells and supported the formation of a small number of colonies, all of which were predominantly eosinophilic. However, it did not support colony formation by spleen cells from 5-FU-treated mice, in which only primitive stem cells had survived, while IL-3 and G-CSF did. Eosinophil- containing colonies were formed from these cells in the presence of IL- 5 and G-CSF together. In contrast, G-CSF alone did not support any eosinophil colonies. The eosinophilopoietic effect of IL-5 was dose- dependent, and was neutralized specifically by anti-IL-5 antibody. To exclude the possibility of interactions with accessory cells in the same culture dish, we replated a small number (200 cells/dish) of enriched hemopoietic progenitors, obtained from blast cell colonies, which were formed by cultivation of spleen cells from 5-FU-treated mice in the presence of IL-3 or G-CSF. From these replated blast cells, eosinophil colonies were induced in dishes containing IL-5 but not in those containing G-CSF alone. From these findings, it was concluded that IL-5 did not act on primitive hemopoietic cells, but on blast cells induced by IL-3 or G-CSF. IL-5 specifically facilitated the terminal differentiation and proliferation of eosinophils. In this respect, the role of IL-5 in eosinophilopoiesis seems to be analogous to erythropoietin, which promotes the terminal differentiation and amplification of erythroid cells. Moreover, IL-5 maintained the viability of mature eosinophils obtained from peritoneal exudate cells of the mice infected with parasites, indicating mature functional eosinophils carried IL-5 receptors. The synergistic effects of IL-5 and colony-stimulating factors on the expansion of eosinophils is supposed to contribute to the urgent mobilization of eosinophils at the time of helminthic infections and allergic responses.

Full Text

The Full Text of this article is available as a PDF (925.8 KB).

Selected References

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

  1. Azuma C., Tanabe T., Konishi M., Kinashi T., Noma T., Matsuda F., Yaoita Y., Takatsu K., Hammarström L., Smith C. I. Cloning of cDNA for human T-cell replacing factor (interleukin-5) and comparison with the murine homologue. Nucleic Acids Res. 1986 Nov 25;14(22):9149–9158. doi: 10.1093/nar/14.22.9149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Begley C. G., Lopez A. F., Nicola N. A., Warren D. J., Vadas M. A., Sanderson C. J., Metcalf D. Purified colony-stimulating factors enhance the survival of human neutrophils and eosinophils in vitro: a rapid and sensitive microassay for colony-stimulating factors. Blood. 1986 Jul;68(1):162–166. [PubMed] [Google Scholar]
  3. Fung M. C., Hapel A. J., Ymer S., Cohen D. R., Johnson R. M., Campbell H. D., Young I. G. Molecular cloning of cDNA for murine interleukin-3. Nature. 1984 Jan 19;307(5948):233–237. doi: 10.1038/307233a0. [DOI] [PubMed] [Google Scholar]
  4. Gough N. M., Gough J., Metcalf D., Kelso A., Grail D., Nicola N. A., Burgess A. W., Dunn A. R. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. 1984 Jun 28-Jul 4Nature. 309(5971):763–767. doi: 10.1038/309763a0. [DOI] [PubMed] [Google Scholar]
  5. Harada N., Kikuchi Y., Tominaga A., Takaki S., Takatsu K. BCGFII activity on activated B cells of a purified murine T cell-replacing factor (TRF) from a T cell hybridoma (B151K12). J Immunol. 1985 Jun;134(6):3944–3951. [PubMed] [Google Scholar]
  6. Harada N., Takahashi T., Matsumoto M., Kinashi T., Ohara J., Kikuchi Y., Koyama N., Severinson E., Yaoita Y., Honjo T. Production of a monoclonal antibody useful in the molecular characterization of murine T-cell-replacing factor/B-cell growth factor II. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4581–4585. doi: 10.1073/pnas.84.13.4581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kajigaya S., Suda T., Suda J., Saito M., Miura Y., Iizuka M., Kobayashi S., Minato N., Sudo T. A recombinant murine granulocyte/macrophage (GM) colony-stimulating factor derived from an inducer T cell line (IH5.5). Functional restriction to GM progenitor cells. J Exp Med. 1986 Oct 1;164(4):1102–1113. doi: 10.1084/jem.164.4.1102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kawasaki E. S., Ladner M. B., Wang A. M., Van Arsdell J., Warren M. K., Coyne M. Y., Schweickart V. L., Lee M. T., Wilson K. J., Boosman A. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science. 1985 Oct 18;230(4723):291–296. doi: 10.1126/science.2996129. [DOI] [PubMed] [Google Scholar]
  9. Metcalf D., Cutler R. L., Nicola N. A. Selective stimulation by mouse spleen cell conditioned medium of human eosinophil colony formation. Blood. 1983 May;61(5):999–1005. [PubMed] [Google Scholar]
  10. Nawa Y., Owhashi M., Imai J., Abe T. Chemotactic reactivity of eosinophils obtained from bone marrow and peritoneal cavity of cyclophosphamide-treated, Toxocara canis-infected mice. Int Arch Allergy Appl Immunol. 1986;80(4):412–416. doi: 10.1159/000234090. [DOI] [PubMed] [Google Scholar]
  11. Nomura H., Imazeki I., Oheda M., Kubota N., Tamura M., Ono M., Ueyama Y., Asano S. Purification and characterization of human granulocyte colony-stimulating factor (G-CSF). EMBO J. 1986 May;5(5):871–876. doi: 10.1002/j.1460-2075.1986.tb04297.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. O'Garra A., Warren D. J., Holman M., Popham A. M., Sanderson C. J., Klaus G. G. Interleukin 4 (B-cell growth factor II/eosinophil differentiation factor) is a mitogen and differentiation factor for preactivated murine B lymphocytes. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5228–5232. doi: 10.1073/pnas.83.14.5228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sanderson C. J., O'Garra A., Warren D. J., Klaus G. G. Eosinophil differentiation factor also has B-cell growth factor activity: proposed name interleukin 4. Proc Natl Acad Sci U S A. 1986 Jan;83(2):437–440. doi: 10.1073/pnas.83.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Suda J., Suda T., Kubota K., Ihle J. N., Saito M., Miura Y. Purified interleukin-3 and erythropoietin support the terminal differentiation of hemopoietic progenitors in serum-free culture. Blood. 1986 Apr;67(4):1002–1006. [PubMed] [Google Scholar]
  15. Suda T., Suda J., Ogawa M. Disparate differentiation in mouse hemopoietic colonies derived from paired progenitors. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2520–2524. doi: 10.1073/pnas.81.8.2520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Suda T., Suda J., Ogawa M. Proliferative kinetics and differentiation of murine blast cell colonies in culture: evidence for variable G0 periods and constant doubling rates of early pluripotent hemopoietic progenitors. J Cell Physiol. 1983 Dec;117(3):308–318. doi: 10.1002/jcp.1041170305. [DOI] [PubMed] [Google Scholar]
  17. Suda T., Suda J., Ogawa M. Single-cell origin of mouse hemopoietic colonies expressing multiple lineages in variable combinations. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6689–6693. doi: 10.1073/pnas.80.21.6689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Swain S. L., Dutton R. W. Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor. J Exp Med. 1982 Dec 1;156(6):1821–1834. doi: 10.1084/jem.156.6.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takatsu K., Harada N., Hara Y., Takahama Y., Yamada G., Dobashi K., Hamaoka T. Purification and physicochemical characterization of murine T cell replacing factor (TRF). J Immunol. 1985 Jan;134(1):382–389. [PubMed] [Google Scholar]
  20. Takatsu K., Kikuchi Y., Takahashi T., Honjo T., Matsumoto M., Harada N., Yamaguchi N., Tominaga A. Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4234–4238. doi: 10.1073/pnas.84.12.4234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Takatsu K., Tanaka K., Tominaga A., Kumahara Y., Hamaoka T. Antigen-induced T cell-replacing factor (TRF). III. Establishment of T cell hybrid clone continuously producing TRF and functional analysis of released TRF. J Immunol. 1980 Dec;125(6):2646–2653. [PubMed] [Google Scholar]
  22. Tanaka J., Torisu M. Anisakis and eosinophil. I. Detection of a soluble factor selectively chemotactic for eosinophils in the extract from Anisakis larvae. J Immunol. 1978 Mar;120(3):745–749. [PubMed] [Google Scholar]
  23. Tsuchiya M., Asano S., Kaziro Y., Nagata S. Isolation and characterization of the cDNA for murine granulocyte colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7633–7637. doi: 10.1073/pnas.83.20.7633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., Cantor H., Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. doi: 10.1073/pnas.81.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES