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.

  • Letter
  • Published:

Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF

Abstract

Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro1,2. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte–macrophage colony-stimulating factor (GM-CSF). Recently, both murine3,4 and human GM-CSF5–7 have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively (refs 5–15; see ref. 8 for a review), little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice16–26, as can human urinary extracts27,28. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans29. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo30,31. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Stanley, E. R. & Jubinsky, P. J. Clin. Haemat. 13, 329–348 (1984).

    CAS  PubMed  Google Scholar 

  2. Metcalf, D. The Hemopoietic Colony Stimulating Factors (Elsevier, Amsterdam, 1984).

    Google Scholar 

  3. Burgess, A. W., Camakaris, J. & Metcalf, D. J. J. biol. Chem. 252, 1998–2003 (1977).

    CAS  Google Scholar 

  4. Grough, N. M. et al. Nature 309, 763–767 (1984).

    Article  ADS  Google Scholar 

  5. Gasson, J. C. et al. Science 226, 1339–1342 (1984).

    Article  ADS  CAS  Google Scholar 

  6. Wong, G. G. et al. Science 228, 810–815 (1985).

    Article  ADS  CAS  Google Scholar 

  7. Wong, G. G. et al. in Cancer Cells Vol. 3 (eds Feramisco, J., Ozanne, B. & Stiles, C.) 235–241 (Cold Spring Harbor Laboratory, New York, 1985).

    Google Scholar 

  8. Metcalf, D. Blood 67, 257–267 (1986).

    CAS  PubMed  Google Scholar 

  9. Weisbart, R. H., Golde, D. W., Clark, S. C., Wong, G. G. & Gasson, J. C. Nature 315, 361–363 (1985).

    Article  ADS  Google Scholar 

  10. Lopez, A. F. et al. J. clin. Invest. (in the press).

  11. Metcalf, D. et al. Blood 67, 37–45 (1986).

    CAS  PubMed  Google Scholar 

  12. Sieff, C. A. et al. Science 230, 1171–1173 (1985).

    Article  ADS  CAS  Google Scholar 

  13. Emerson, S. G. et al. J. clin. Invest. 76, 1286–1290 (1985).

    Article  CAS  Google Scholar 

  14. Donahue, R. E. et al. Blood 66, 1479–1481 (1985).

    CAS  PubMed  Google Scholar 

  15. Sieff, C. A., Emerson, S. G., Mufson, A., Gesner, T. G. & Nathan, D. G. J. clin. Invest. 77, 74–81 (1986).

    Article  CAS  Google Scholar 

  16. Asano, S. et al. Blood 49, 845–852 (1977).

    CAS  PubMed  Google Scholar 

  17. Burlington, H., Cronkite, E. P., Laissne, J. A., Reincke, U. & Shadduck, R. K. Proc. Soc. exp. Biol. Med. 153, 86–92 (1977).

    Article  Google Scholar 

  18. Suda, T., Miura, Y., Mizoguchi, H., Kubota, K. & Takaku, F. Br. J. Cancer 41, 980–984 (1980).

    Article  CAS  Google Scholar 

  19. Lee, M. Y., Sperlin, A. & Dale, D. C. Expl Hemat. 8, 249–255 (1980).

    CAS  Google Scholar 

  20. Mizoguchi, H., Suda, T., Miura, Y., Kubota, K. & Takaku, F. Expl Hemat. 10, 874–880 (1982).

    CAS  Google Scholar 

  21. Motoyoshi, K., Suda, T., Takau, F. & Miura, Y. Blood 62, 980–987 (1983).

    CAS  PubMed  Google Scholar 

  22. Bessho, M., Hiroshima, K., Ando, K., Nara, N. & Momoi, H. Acta haemat. Jap. 47, 21–33 (1984).

    CAS  PubMed  Google Scholar 

  23. Yunis, A. A., Jimenez, J. J., Wu, M. & Andreotti, P. E. Expl Hemat. 12, 838–843 (1984).

    CAS  Google Scholar 

  24. Lee, M. Y. & Lottsfelt, J. L. Blood 64, 499–506 (1984).

    CAS  PubMed  Google Scholar 

  25. Miyanomae, T. et al. Gann 76, 352–358 (1985).

    CAS  PubMed  Google Scholar 

  26. Johnson, G. R., Whitehead, R. & Nicola, N. A. Int. J. Cell Cloning 3, 91–105 (1985).

    Article  CAS  Google Scholar 

  27. Kohsaki, M. et al. Proc. natn. Acad. Sci. U.S.A. 80, 3802–3906 (1983).

    Article  ADS  CAS  Google Scholar 

  28. Metcalf, D. & Stanley, E. R. Br. J. Haemal. 21, 481–492 (1971).

    Article  CAS  Google Scholar 

  29. Motoyoshi, K., Takaku, F. & Miura, Y. Blood 62, 685–688 (1983).

    CAS  PubMed  Google Scholar 

  30. Kindler, V. et al. Proc. natn. Acad. Sci. U.S.A. 83, 1001–1005 (1986).

    Article  ADS  CAS  Google Scholar 

  31. Metcalf, D. et al. (in preparation).

  32. Golde, D. W. & Hocking, W. G. in Hematopoietic Cell Differentation (eds Golde, D. W., Cline, M. J., Metcalf, D. & Fox, C. F.) 375–383 (Academic, New York, 1978).

    Google Scholar 

  33. Linch, D. C. & Nathan, D. G. Nature 312, 775–777 (1984).

    Article  ADS  CAS  Google Scholar 

  34. Shargel, L. & Yu, A. B. C. Applied Biopharmaceutics and Pharmacokinetics (Appleton-Century-Crofts, Norwalk, Connecticut, 1985).

    Google Scholar 

  35. Krystal, G. Expl Hemat. 11, 649–666 (1983).

    CAS  Google Scholar 

  36. Letvin, N. L. & King, N. W. Adv. vet. Sci. 28, 237–265 (1984).

    Article  CAS  Google Scholar 

  37. Letvin, N. L. et al. J. Virol. 52, 683–686 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. MacKenzie, M. et al. Lab. Anim. Sci. 36, 14–19 (1986).

    CAS  PubMed  Google Scholar 

  39. Young, N. & Mortimer, P. Blood 63, 729–737 (1984).

    CAS  PubMed  Google Scholar 

  40. Spivak, J. L., Bender, B. S. & Quinn, T. C. Am. J. Med. 77, 224–228 (1984).

    Article  CAS  Google Scholar 

  41. Zon, L. I. & Groopman, J. E. (in preparation).

  42. Gasson, J. C., Chen, I. S. Y., Westbrook, C. A. & Golde, D. W. Normal and Neoplastic Hematopoiesis (eds Golde, D. W. & Marks, P. A.) 129–139 (Liss, New York, 1983).

    Google Scholar 

  43. Iscove, N. W., Sieber, F. & Winterhalter, K. W. J. cell. Physiol. 83, 309–320 (1974).

    Article  CAS  Google Scholar 

  44. Committee on Care and Use of Laboratory Animals DHEW Publ. NIH 78–23 (revised 1978).

  45. Griffin, J. D. et al. Blood 63, 904–911 (1984).

    CAS  PubMed  Google Scholar 

  46. Daniel, M. D. et al. Science 223, 602–605 (1984).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donahue, R., Wang, E., Stone, D. et al. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. Nature 321, 872–875 (1986). https://doi.org/10.1038/321872a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/321872a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing