Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Animal Models

The multi-organ origin of interleukin-5 in the mouse

Abstract

Murine Ba/F3 cells were transfected with cDNA for the α-chain of the murine interleukin-5 (IL-5) receptor and cloned lines of these cells were able to proliferate in response to as little as 2.5 pg/ml of IL-5. The bioassay was demonstrated to be specific for IL-5 and was able to measure IL-5 produced in culture by organs from adult C57BL/6 and BALB/c mice. The highest levels of IL-5 were produced by lung tissue but thymus and bladder consistently produced IL-5 and more variable production was observed by the heart, spleen, muscle, bone shaft, uterus and testes. Bone marrow cells produced no detectable IL-5. Observed levels of production of IL-5 were similar when using organs from mice lacking high-affinity receptors for IL-5 and from nu/nu, RAG-1−/− and NOD/SCID mice lacking T lymphocytes. In inflammatory peritoneal exudates induced by the injection of casein plus bacteria, levels of induced IL-5 were higher if the mice lacked high-affinity receptors for IL-5. The data indicate that T lymphocytes are not the dominant cellular source of IL-5 in organ-conditioned media and that local IL-5 production can occur with a wide range of normal murine organs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. McCarthy JH, Nicola N, Szelag G, Garson OM . Studies on eosinophil colonies grown from leukaemic and non-leukaemic patients Leuk Res 1980 4: 415–426

    Article  CAS  PubMed  Google Scholar 

  2. Le Beau MM, Larson RA, Bitter MA, Vardiman JW, Golomb HM, Rowley JD . Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia New Engl J Med 1983 309: 630–633

    Article  CAS  Google Scholar 

  3. Ema H, Kitano K, Suda T, Sato Y, Muroi K, Ohta M, Yoshida M, Sakamoto S, Eguchi M, Miura Y . In vitro differentiation of leukemic cells to eosinophils in the presence of interleukin-5 in two cases of acute myeloid leukemia with the translocation (8:21)(q22;q22) Blood 1990 75: 350–356

    CAS  Google Scholar 

  4. Major RH, Leger LH . Marked eosinophilia in Hodgkin's disease JAMA 1939 112: 2601–2602

    Article  Google Scholar 

  5. Metcalf D, Burgess AW . Johnson GR, Nicola NA, Nice EC, DeLamarter J, Thatcher DR, Mermod J-J. In vitro actions on hemopoietic cells of recombinant murine GM-CSF purified after production in Escherichia coli: comparison with purified native GM-CSF J Cell Physiol 1986 128: 421–431

    Article  CAS  PubMed  Google Scholar 

  6. Metcalf D, Begley CG, Nicola NA, Johnson GR . Quantitative responsiveness of murine hemopoietic populations in vitro and in vivo to recombinant multi-CSF (IL-3) Exp Hematol 1987 15: 288–295

    CAS  PubMed  Google Scholar 

  7. Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ . Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells J Exp Med 1986 163: 1085–1099

    Article  CAS  PubMed  Google Scholar 

  8. Metcalf D, Willson TA, Hilton DJ, Di Rago L, Mifsud S . Production of hematopoietic regulatory factors in cultures of adult and fetal mouse organs: measurement by specific bioassays Leukemia 1995 9: 1556–1564

    CAS  PubMed  Google Scholar 

  9. Lang RA, Metcalf D, Cuthbertson RA, Lyons I, Stanley E, Kelso A, Kannourakis G, Williamson DJ, Klintworth GK, Gonda TJ, Dunn AR . Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness and a fatal syndrome of tissue damage Cell 1987 51: 675–686

    Article  CAS  PubMed  Google Scholar 

  10. Dent LA, Strath M, Mellor AL, Sanderson CJ . Eosinophilia in transgenic mice expressing interleukin 5 J Exp Med 1990 172: 1425–1431

    Article  CAS  PubMed  Google Scholar 

  11. Stanley E, Lieschke GJ, Grail D, Metcalf D, Hodgson G, Gall JA, Maher DW, Cebon J, Sinickas V, Dunn AR . Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology Proc Natl Acad Sci USA 1994 91: 5592–5596

    Article  CAS  PubMed  Google Scholar 

  12. Kopf M, Brombacher F, Hodgkin PD, Ramsay AJ, Milbourne EA, Dai WJ, Ovington KS, Behm CA, Kohler G, Young IG, Matthaei KI . IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses Immunity 1996 4: 15–24

    Article  CAS  Google Scholar 

  13. Robb L, Drinkwater CC, Metcalf D, Li R, Köntgen F, Nicola NA, Begley CG . Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte–macrophage colony-stimulating factor and interleukins 3 and 5 Proc Natl Acad Sci USA 1995 92: 9565–9569

    Article  CAS  Google Scholar 

  14. Nishii K, Kita K, Nadim M, Miwa H, Ohoishi K, Yamaguchi M, Shirakawa S . Expression of interleukin-5 receptors on acute myeloid leukaemia cells: association with immunophenotype and karyotype Br J Haematol 1995 91: 169–172

    Article  CAS  Google Scholar 

  15. Schimpl A, Wecker E . Replacement of T-cell function by a T-cell product Nat New Biol 1972 237: 15–17

    Article  CAS  PubMed  Google Scholar 

  16. Metcalf D, Cutler RL, Nicola NA . Selective stimulation by mouse spleen cell conditioned medium of human eosinophil colony formation Blood 1983 61: 999–1005

    CAS  PubMed  Google Scholar 

  17. Kinashi T, Harada N, Severinson E, Tanabe T, Sideras P, Konishi M, Azuma C, Tominaga A, Bergsted-Lindqvist S, Takahashi M, Matsuda F, Yaoita Y, Takatsu K, Honjo T . Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II Nature 1986 324: 70–73

    Article  CAS  PubMed  Google Scholar 

  18. Garlisi CG, Falcone A, Kung TT, Stelts D, Pennline KJ, Beavis AJ, Smith SR, Egan RW, Umland SP . T cells are necessary for Th2 cytokine production and eosinophil accumulation in airways of antigen-challenged allergic mice Clin Immunol Immunopathol 1995 75: 75–83

    Article  CAS  Google Scholar 

  19. Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP, Paul WE . Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores Nature 1989 339: 64–67

    Article  CAS  PubMed  Google Scholar 

  20. Desreumaux P, Janin A, Colombel JF, Prin L, Plumas J, Emilie D, Torpier G, Capron A, Capron M . Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease J Exp Med 1992 175: 293–296

    Article  CAS  PubMed  Google Scholar 

  21. Warren HS, Kinnear BF, Phillips JH, Lanier LL . Production of IL-5 by human NK cells and regulation of IL-5 secretion by IL-4, IL-10, and IL-12 J Immunol 1995 154: 5144–5152

    CAS  PubMed  Google Scholar 

  22. Samoszuk M, Nansen L . Detection of interleukin-5 messenger RNA in Reed–Sternberg cells of Hodgkin's disease with eosinophilia Blood 1990 75: 13–16

    CAS  PubMed  Google Scholar 

  23. Paul CC, Keller JR, Armpriester JM, Baumann MA . Epstein–Barr virus transformed B lymphocytes produce interleukin-5 Blood 1990 75: 1400–1403

    CAS  PubMed  Google Scholar 

  24. Salvi S, Semper A, Blomberg A, Holloway J, Jaffar Z, Papi A, Teran L, Polosa R, Kelly F, Sandstrom T, Holgate S, Frew A . Interleukin-5 production by human airway epithelial cells Am J Respir Cell Mol Biol 1999 20: 984–991

    Article  CAS  PubMed  Google Scholar 

  25. Metcalf D, Willson T, Rossner M, Lock P . Receptor insertion into factor-dependent murine cell lines to develop specific bioassays for murine G-CSF and M-CSF and human GM-CSF Growth Factors 1994 11: 145–152

    Article  CAS  PubMed  Google Scholar 

  26. Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G . A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF Cell 1991 66: 1175–1184

    Article  CAS  PubMed  Google Scholar 

  27. Ihle JN, Keller J, Henderson L, Klein F, Palaszynski E . Procedures for the purification of interleukin 3 to homogeneity J Immunol 1982 129: 2431–2436

    CAS  PubMed  Google Scholar 

  28. Metcalf D, Robb L, Dunn AR, Mifsud S, Di Rago L . Role of granulocyte–macrophage colony-stimulating factor and granulocyte colony-stimulating factor in the development of an acute neutrophil inflammatory response in mice Blood 1996 88: 3755–3764

    CAS  PubMed  Google Scholar 

  29. Begley CG, Lopez AF, Nicola NA, Warren DJ, Vadas MA, Sanderson CJ, 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 68: 162–166

    CAS  PubMed  Google Scholar 

  30. Castro AG, Silva RA, Minoprio P, Appelberg R . In vivo evidence for a non-T cell origin of interleukin-5 Scand J Immunol 1995 41: 288–292

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to Dr J-G Zhang, Bronwyn Roberts and Wendy Carter for their assistance in producing purified recombinant murine IL-5. This work was supported by the Carden Fellowship Fund of the Anti-Cancer Council of Victoria, the National Health and Medical Research Council, Canberra and the National Institutes of Health, Bethesda, Grant No. CA-22556.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ryan, P., Willson, T., Alexander, W. et al. The multi-organ origin of interleukin-5 in the mouse. Leukemia 15, 1248–1255 (2001). https://doi.org/10.1038/sj.leu.2402173

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402173

Keywords

Search

Quick links