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. 1987 Dec 1;166(6):1851–1860. doi: 10.1084/jem.166.6.1851

Recombinant human macrophage colony-stimulating factor (M-CSF) requires subliminal concentrations of granulocyte/macrophage (GM)-CSF for optimal stimulation of human macrophage colony formation in vitro

PMCID: PMC2188800  PMID: 2445896

Abstract

Human macrophage colony-stimulating factor (M-CSF or CSF-1), either in purified or in recombinant form, is able to generate macrophagic colonies in a murine bone marrow colony assay, but only stimulates small macrophagic colonies of 40-50 cells in a human bone marrow colony assay. We report here that recombinant human granulocytic/macrophage colony stimulating factor (rhGM-CSF) at concentrations in the range of picograms enhances the responsiveness of bone marrow progenitors to M- CSF activity, resulting in an increased number of macrophagic colonies of up to 300 cells. Polyclonal antiserum against M-CSF did not alter colony formation of bone marrow progenitors incubated with GM-CSF at optimal concentration (1-10 ng/ml) for these in vitro assays. Thus, GM- CSF at higher concentrations (nanogram range) can by itself, elicit macrophagic colonies, and at lower concentrations (picogram range) acts to enhance the responsiveness of these progenitors to M-CSF.

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Selected References

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  1. Ben-Avram C. M., Shively J. E., Shadduck R. K., Waheed A., Rajavashisth T., Lusis A. J. Amino-terminal amino acid sequence of murine colony-stimulating factor 1. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4486–4489. doi: 10.1073/pnas.82.13.4486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clark-Lewis I., Kent S. B., Schrader J. W. Purification to apparent homogeneity of a factor stimulating the growth of multiple lineages of hemopoietic cells. J Biol Chem. 1984 Jun 25;259(12):7488–7494. [PubMed] [Google Scholar]
  3. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  4. Cutler R. L., Metcalf D., Nicola N. A., Johnson G. R. Purification of a multipotential colony-stimulating factor from pokeweed mitogen-stimulated mouse spleen cell conditioned medium. J Biol Chem. 1985 Jun 10;260(11):6579–6587. [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. Lopez A. F., To L. B., Yang Y. C., Gamble J. R., Shannon M. F., Burns G. F., Dyson P. G., Juttner C. A., Clark S., Vadas M. A. Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3. Proc Natl Acad Sci U S A. 1987 May;84(9):2761–2765. doi: 10.1073/pnas.84.9.2761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
  10. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  11. Rajavashisth T. B., Eng R., Shadduck R. K., Waheed A., Ben-Avram C. M., Shively J. E., Lusis A. J. Cloning and tissue-specific expression of mouse macrophage colony-stimulating factor mRNA. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1157–1161. doi: 10.1073/pnas.84.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Shieh J. H., Cini J. K., Wu M. C., Yunis A. A. Purification and characterization of human colony-stimulating factor 1 from human pancreatic carcinoma (MIA PaCa-2) cells. Arch Biochem Biophys. 1987 Feb 15;253(1):205–213. doi: 10.1016/0003-9861(87)90653-9. [DOI] [PubMed] [Google Scholar]
  14. Sieff C. A. Hematopoietic growth factors. J Clin Invest. 1987 Jun;79(6):1549–1557. doi: 10.1172/JCI112988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stanley E. R., Bartocci A., Patinkin D., Rosendaal M., Bradley T. R. Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1. Cell. 1986 Jun 6;45(5):667–674. doi: 10.1016/0092-8674(86)90781-6. [DOI] [PubMed] [Google Scholar]
  16. Stanley E. R., Heard P. M. Factors regulating macrophage production and growth. Purification and some properties of the colony stimulating factor from medium conditioned by mouse L cells. J Biol Chem. 1977 Jun 25;252(12):4305–4312. [PubMed] [Google Scholar]
  17. 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]
  18. Welte K., Platzer E., Lu L., Gabrilove J. L., Levi E., Mertelsmann R., Moore M. A. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1526–1530. doi: 10.1073/pnas.82.5.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wong G. G., Temple P. A., Leary A. C., Witek-Giannotti J. S., Yang Y. C., Ciarletta A. B., Chung M., Murtha P., Kriz R., Kaufman R. J. Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding the human urinary protein. Science. 1987 Mar 20;235(4795):1504–1508. doi: 10.1126/science.3493529. [DOI] [PubMed] [Google Scholar]
  20. Wu M., Cini J. K., Yunis A. A. Purification of a colony-stimulating factor from cultured pancreatic carcinoma cells. J Biol Chem. 1979 Jul 25;254(14):6226–6228. [PubMed] [Google Scholar]

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