Skip to main content
PMC home page
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):4670–4674. doi: 10.1073/pnas.87.12.4670

Low-affinity placenta-derived receptors for human granulocyte-macrophage colony-stimulating factor can deliver a proliferative signal to murine hemopoietic cells.

D Metcalf 1, N A Nicola 1, D P Gearing 1, N M Gough 1
PMCID: PMC54178  PMID: 2162053

Abstract

Retrovirally mediated introduction of a cDNA encoding a placenta-derived low-affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) into murine FDC-P1 hemopoietic cells allowed these cells to proliferate when stimulated by human GM-CSF. The expressed human receptors on cloned lines were of low affinity (Kd = 4-6 nM), were internalized, and did not interact with endogenous GM-CSF receptors. Concentrations of human GM-CSF of 6.5-13 nM were required to stimulate 50% maximal colony formation versus a concentration of murine GM-CSF of 6 pM; this difference is comparable with the difference in relative affinities of the human and murine receptors for their respective ligands. If maintained in murine GM-CSF, cells able to bind or respond to human GM-CSF were rapidly lost due to transcriptional inactivation of the inserted cDNA. The observations indicate that low-affinity receptors for human GM-CSF can deliver a proliferative signal in appropriate cells and that the signaling mechanisms are not species-specific.

Full text

PDF
4670

Images in this article

4671Image
on p.4671
4671Image
on p.4671

Selected References

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

  1. Bernard O., Reid H. H., Bartlett P. F. Role of the c-myc and the N-myc proto-oncogenes in the immortalization of neural precursors. J Neurosci Res. 1989 Sep;24(1):9–20. doi: 10.1002/jnr.490240104. [DOI] [PubMed] [Google Scholar]
  2. Bussolino F., Wang J. M., Defilippi P., Turrini F., Sanavio F., Edgell C. J., Aglietta M., Arese P., Mantovani A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 1989 Feb 2;337(6206):471–473. doi: 10.1038/337471a0. [DOI] [PubMed] [Google Scholar]
  3. Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
  4. Chang S. M., Wager-Smith K., Tsao T. Y., Henkel-Tigges J., Vaishnav S., Caskey C. T. Construction of a defective retrovirus containing the human hypoxanthine phosphoribosyltransferase cDNA and its expression in cultured cells and mouse bone marrow. Mol Cell Biol. 1987 Feb;7(2):854–863. doi: 10.1128/mcb.7.2.854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dedhar S., Gaboury L., Galloway P., Eaves C. Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9253–9257. doi: 10.1073/pnas.85.23.9253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elliott M. J., Vadas M. A., Eglinton J. M., Park L. S., To L. B., Cleland L. G., Clark S. C., Lopez A. F. Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor show common biological effects and binding characteristics on human monocytes. Blood. 1989 Nov 15;74(7):2349–2359. [PubMed] [Google Scholar]
  8. Emerman M., Temin H. M. Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell. 1984 Dec;39(3 Pt 2):449–467. [PubMed] [Google Scholar]
  9. Evans D. B., Bunning R. A., Russell R. G. The effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on human osteoblast-like cells. Biochem Biophys Res Commun. 1989 Apr 28;160(2):588–595. doi: 10.1016/0006-291x(89)92473-x. [DOI] [PubMed] [Google Scholar]
  10. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  11. Gasson J. C., Kaufman S. E., Weisbart R. H., Tomonaga M., Golde D. W. High-affinity binding of granulocyte-macrophage colony-stimulating factor to normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1986 Feb;83(3):669–673. doi: 10.1073/pnas.83.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  14. Gough N. M. Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Anal Biochem. 1988 Aug 15;173(1):93–95. doi: 10.1016/0003-2697(88)90164-9. [DOI] [PubMed] [Google Scholar]
  15. Johnson G. R., Gonda T. J., Metcalf D., Hariharan I. K., Cory S. A lethal myeloproliferative syndrome in mice transplanted with bone marrow cells infected with a retrovirus expressing granulocyte-macrophage colony stimulating factor. EMBO J. 1989 Feb;8(2):441–448. doi: 10.1002/j.1460-2075.1989.tb03396.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lopez A. F., Eglinton J. M., Gillis D., Park L. S., Clark S., Vadas M. A. Reciprocal inhibition of binding between interleukin 3 and granulocyte-macrophage colony-stimulating factor to human eosinophils. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7022–7026. doi: 10.1073/pnas.86.18.7022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Magli M. C., Dick J. E., Huszar D., Bernstein A., Phillips R. A. Modulation of gene expression in multiple hematopoietic cell lineages following retroviral vector gene transfer. Proc Natl Acad Sci U S A. 1987 Feb;84(3):789–793. doi: 10.1073/pnas.84.3.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
  19. Morstyn G., Lieschke G. J., Sheridan W., Layton J., Cebon J. Pharmacology of the colony-stimulating factors. Trends Pharmacol Sci. 1989 Apr;10(4):154–159. doi: 10.1016/0165-6147(89)90168-5. [DOI] [PubMed] [Google Scholar]
  20. Nicola N. A., Peterson L., Hilton D. J., Metcalf D. Cellular processing of murine colony-stimulating factor (Multi-CSF, GM-CSF, G-CSF) receptors by normal hemopoietic cells and cell lines. Growth Factors. 1988;1(1):41–49. doi: 10.3109/08977198809000245. [DOI] [PubMed] [Google Scholar]
  21. Park L. S., Friend D., Price V., Anderson D., Singer J., Prickett K. S., Urdal D. L. Heterogeneity in human interleukin-3 receptors. A subclass that binds human granulocyte/macrophage colony stimulating factor. J Biol Chem. 1989 Apr 5;264(10):5420–5427. [PubMed] [Google Scholar]
  22. Walker F., Burgess A. W. Specific binding of radioiodinated granulocyte-macrophage colony-stimulating factor to hemopoietic cells. EMBO J. 1985 Apr;4(4):933–939. doi: 10.1002/j.1460-2075.1985.tb03721.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Walker F., Nicola N. A., Metcalf D., Burgess A. W. Hierarchical down-modulation of hemopoietic growth factor receptors. Cell. 1985 Nov;43(1):269–276. doi: 10.1016/0092-8674(85)90032-7. [DOI] [PubMed] [Google Scholar]
  24. Wegmann T. G., Athanassakis I., Guilbert L., Branch D., Dy M., Menu E., Chaouat G. The role of M-CSF and GM-CSF in fostering placental growth, fetal growth, and fetal survival. Transplant Proc. 1989 Feb;21(1 Pt 1):566–568. [PubMed] [Google Scholar]
  25. Williams D. A., Orkin S. H., Mulligan R. C. Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2566–2570. doi: 10.1073/pnas.83.8.2566. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES