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Developmental regulation of granulocyte-macrophage colony-stimulating factor production during human monocyte-to-macrophage maturation

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Summary

Cells of the macrophage lineage are a major source of various cytokines and hematopoietic growth factors. With regard to the growth factors acting on cells of their own lineage, macrophage colony-stimulating factor (M-CSF) has been proven to be secreted by monocytes (MO) and macrophages (MAC), whereas the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human MO/MAC is under debate. Here we report that in elutriation-purified MO, as well as in MAC derived from cultured MO, GM-CSF m-RNA was regularly induced by LPS. In MO the GM-CSF message was still detectable 18h after stimulation under serum-free conditions, but in contrast was already lost at this time point in MAC. Secreted GM-CSF protein was detected in the culture medium using a sandwich ELISA. Furthermore, a factor-dependent cell line (M-07) was used for a biological assay. Here, a neutralizing anti GM-CSF antibody specifically blocked the proliferation-inducing activity of MO/MAC supernatants. Whereas only small amounts of GM-CSF were detected in MO, its secretion increased severalfold upon MO-to-MAC differentation in vitro. A similar increase upon in vitro maturation of MO was observed for the production of granulocyte colony-stimulating factor. The highest amounts of GM-CSF (up to 2.8 ng/106 cells) were produced by MAC that had been derived from MO cultured under serum-free conditions in the presence of 0.5 mg/ml albumin as the only medium supplement.

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References

  1. Andreesen R, Picht J, Löhr GW (1983) Primary cultures of human blood-borne, macrophages grown on hydrophobic Teflon membranes. J Immunol Meth 56: 295–304

    Google Scholar 

  2. Andreesen R, Brugger W, Scheibenbogen C, Kreutz M, Leser HG, Rehm A, Löhr GW (1990) Surface phenotype analysis of human monocyte-to-macrophage maturation. J Leukoc Biol 47: 490–497

    PubMed  Google Scholar 

  3. Avanzi GC, Lista P, Giovinazzo B, Miniero R, Saglio G, Benetton G, Coda R, Cattoretti G, Pegoraro L (1988) Selective growth response to IL-3 of a human leukaemic cell line with megacarioblastic features. Br J Haematol 69: 359–366

    PubMed  Google Scholar 

  4. Baggiolini M, Walz A, Kunkel SL (1989) Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest 84: 1045–1049

    PubMed  Google Scholar 

  5. Becker S, Warren MK, Haskill S (1987) Colony-stimulating factor induced monocyte survival and differentiation into macrophages in serum-free cultures. J Immunol 139: 3703–3709

    PubMed  Google Scholar 

  6. Becker S, Devlin RB, Haskill JS (1989) Differential production of tumor necrosis factor, macrophage colony-stimulating factor, and interleukin 1 by human alveolar macrophages. J Leukoc Biol 45: 353–361

    PubMed  Google Scholar 

  7. Brugger W, Kreutz M, Andreesen R (1991) Macrophage colonystimulating factor is required for human monocyte survival and acts as a cofactor for their terminal differentiation to macrophages in vitro. J Leukoc Biol 49: 483–488

    PubMed  Google Scholar 

  8. Chomzynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159

    PubMed  Google Scholar 

  9. Church GM, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci 81: 1991–1995

    PubMed  Google Scholar 

  10. Clark, SC, Kamen R (1987) The human hematopoietic colony-stimulating factors. Science 236: 1229–1237

    PubMed  Google Scholar 

  11. Eierman DF, Johnson CE, Haskill JS (1989) Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates. J Immunol 142: 1970–1976

    PubMed  Google Scholar 

  12. Gough NM (1990) The hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor. In: Habenicht A (ed) Growth factors, differentiation factors, and cytokines. Springer, Berlin, Heidelberg, New York, p 177

    Google Scholar 

  13. Hart PH, Whitty GA, Piccoli DS, Hamilton JA (1988) Synergistic actions of human monocytes by granulocyte-macrophage colony-stimulating factor and IFN-gamma. J Immunol 141: 1516–1521

    PubMed  Google Scholar 

  14. Haskill S, Johnson C, Eierman D, Becker S, Warren K (1988) Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol 140: 1690–1694

    PubMed  Google Scholar 

  15. Heidenreich S, Gong JH, Schmidt A, Nain M, Gemsa D (1989) Macrophage activation by granulocyte-macrophage colony-stimulating factor. J Immunol 143: 1198–1205

    PubMed  Google Scholar 

  16. Kato T, Inaba K, Ogawa Y, Inaba M, Shimizu S, Ikehara S, Sudo T, Muramatsu S (1990) Granulocyte-macrophage colony-stimulating factor enhances macrophage accessory function in Con-A-stimulated T-cell proliferation. Cell Immunol 130: 490–500

    PubMed  Google Scholar 

  17. Kreutz M, Krause SW, Hennemann B, Rehm A, Andreesen R (1992) Macrophage heterogeneity and differentiation: defined serum-free culture conditions induce different types of macrophages in vitro. Res Immunol 143: 107–115

    PubMed  Google Scholar 

  18. Lee MT, Kaushansky K, Ralph P, Ladner MB (1990) Differential expression of M-CSF, G-CSF, and GM-CSF by human monocytes. J Leukoc Biol 47: 275–282

    PubMed  Google Scholar 

  19. Markovicz S, Engelman EG (1990) Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro. J Clin Invest 85: 955–961

    PubMed  Google Scholar 

  20. Munn DH, Cheung NKV (1989) Antibody-dependent anti-tumor cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. J Exp Med 170: 511–526

    PubMed  Google Scholar 

  21. Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79: 319–326

    PubMed  Google Scholar 

  22. Oster W, Lindemann A, Mertelsmann R, Herrmann F (1989) Production of macrophage-, granulocyte-, granulocyte-macro-phage- and multi-colony-stimulating factor by peripheral blood cells. Eur J Immunol 19: 543–547

    PubMed  Google Scholar 

  23. Reske-Kunz AB, Fischer HG, Reske K (1988) Induction of antigen presentation capacity and MHC class-II gene expression in bone marrow macrophages derived from GM-CSF-supple-mented in vitro cultures. Behring Inst Mitt 9(83): 258–264

    Google Scholar 

  24. Roberts PJ, Devereux S, Pilkington GR, Linch DC (1990) Fc gamma RII-mediated superoxide production by phagocytes is augmented by GM-CSF without a change in Fc gamma RII expression. J Leukoc Biol 48: 247–257

    PubMed  Google Scholar 

  25. Scheibenbogen C, Zenke G, Faggs B, Motoyoshi K, Kanz L, Sawert H, Brugger W, Andreesen R (1990) Secretion of colony-stimulating factor for macrophages (M-CSF) and granulocyte/ macrophages (GM-CSF) is developmentally regulated in human macrophages. In: Freund M, Link H, Welte K (eds) Cytokines in hemopoiesis, oncology, and AIDS. Springer, Berlin, Heidelberg, New York, p 45

    Google Scholar 

  26. Scheibenbogen C, Andreesen R (1991) Developmental regulation of the cytokine repertoire in human macrophages: IL-1, IL-6, TNF-α, and M-CSF. J Leukoc Biol 50: 35–42

    PubMed  Google Scholar 

  27. Sieff CA, Niemeyer CM, Mentzer SJ, Faller DJ (1988) Interleukin-1, tumor necrosis factor, and the production of colony-stimulating factors by cultured mesenchymal cells. Blood 72: 1316–1323

    PubMed  Google Scholar 

  28. Thorens B, Mermod JJ, Vassalli P (1987) Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. Cell 48: 671–679

    PubMed  Google Scholar 

  29. Weite K, Platzer E (1990) Granulocyte colony-stimulating factor. In: Habenicht A (ed) Growth factors, differentiation factors, and cytokines. Springer, Berlin, Heidelberg, New York, p 201

    Google Scholar 

  30. Wewers MD, Herzyk DJ (1989) Alveolar macrophages differ from monocytes in human IL-1β release. J Immunol 143: 1635–1641

    PubMed  Google Scholar 

  31. Wong GG, Witek JS, Temple PA, Wilkens KM, Leary AC, Luxenberg DP, Jones SS, Brown EJ, Kay RM, Orr EC, Shoemaker C, Golde DW, Kaufman RJ, Hewick RM, Wang EA, Clark SC (1985) Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins Science 228: 810–815

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik I der Universität Freiburg, Freiburg, Federal Republic of Germany

    S. W. Krause, M. Kreutz & R. Andreesen

  2. Sandoz AG, Basel, Switzerland

    G. Zenke

Authors
  1. S. W. Krause
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  2. M. Kreutz
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  3. G. Zenke
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  4. R. Andreesen
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This work was supported by theDeutsche Forschungsgemeinschaft (AN 111).

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Krause, S.W., Kreutz, M., Zenke, G. et al. Developmental regulation of granulocyte-macrophage colony-stimulating factor production during human monocyte-to-macrophage maturation. Ann Hematol 64, 190–195 (1992). https://doi.org/10.1007/BF01696222

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  • DOI: https://doi.org/10.1007/BF01696222

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