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The effect of interleukin-4 with or without mast cell growth factor on peripheral blood granulocyte-macrophage colony-forming cells in healthy controls and in myeloproliferative disorders

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Abstract

The effect of interleukin-4 (IL-4) on peripheral blood (PB) granulocyte-macrophage (GM) progenitors was investigated in the presence and absence of other hematopoietic growth factors, especially the mast cell growth factor (MGF), in eight healthy controls and in 26 patients with myeloproliferative disorders (MPDs) using a clonogenic cell culture assay. In the controls IL-4 was effective alone, stimulating myeloid colony growth in 50%, while MGF had no effect as a single factor. When either IL-4 or MGF was added to the combination of IL-3, GM-CSF, G-CSF, and IL-6, a statistically significant increase in the colony number was observed. The most potent colony formation took place when all these GFs were combined. In the combinations, the effect of IL-4 was additive, while MGF worked synergistically. In the MPDs, IL-4 had no effect at all on the GM progenitors in the whole group of MPDs or on the different subgroups.

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References

  1. Brantschen S, Gauchat JF, De Weck AL, Stadler BM (1989) Regulatory effect of recombinant interleukin (IL-3) and IL-4 on cytokine gene expression of bone marrow and peripheral blood mononuclear cells. Eur J Immunol 19:2017–2023

    PubMed  Google Scholar 

  2. Broxmeyer HE, Lu L, Cooper S, Tushinski R, Mochizuki D, Rubin BY, Gillis S, Williams DE (1988) Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. J Immunol 141:3852–3862

    PubMed  Google Scholar 

  3. Broxmeyer HE, Cooper S, Lu L, Hangoc G, Anderson D, Cosman D, Lyman SD, Williams DE (1991) Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. Blood 77:2142–2149

    PubMed  Google Scholar 

  4. Budel LM, Delwel R, Buitenen C, Hoogerbrugge H, Löwenberg B (1993) Effects of mast cell growth factor on acute myeloid leukemia cells in vitro: effects of combinations with other cytokines. Leukemia 7:426–437

    PubMed  Google Scholar 

  5. Buick RD, Till JE, McCulloch EA (1977) Colony assay for proliferative blast cells circulating in myeloblastic leukemia. Lancet 1:862–863

    Google Scholar 

  6. Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 [Suppl 97]:77–89

    PubMed  Google Scholar 

  7. Caracciolo D, Clark S, Rovera G (1989) Differential activity of recombinant colony-stimulating factors in supporting proliferation of human peripheral blood and bone marrow myeloid progenitors in culture. Br J Haematol 72:306–311

    PubMed  Google Scholar 

  8. Estrov Z, Markowitz AB, Kurzrock R, Wetzler M, Kantarjian HM, Ferrajoli A, Gutterman JU, Talpaz M (1993) Suppression of chronic myelogenous leukemia colony growth by interleukin-4. Leukemia 7:214–220

    PubMed  Google Scholar 

  9. Fernandez-Botran R, Kramer PH, Diamanstein T, Uhr JW, Vitetta ES (1986) B-cell stimulatory factor 1 (BSF-1) promotes growth of T-cell lines. J Exp Med 164:580–593

    PubMed  Google Scholar 

  10. Ferrajoli A, Zipf TF, Talpaz M, Felix EA, Estrov Z (1993) Growth factors controlling interleukin-4 action on hematopoietic progenitors. Ann Hematol 67:277–284

    PubMed  Google Scholar 

  11. Hoffman R, Silverstein MN (1991) Agnogenic myeloid metaplasia. In: Hoffman R, Bentz EJ jr, Shattil SJ, Furie B, Cohen HJ (eds) Hematology, basic principles and practice. Churchill Livingstone, New York, pp 870–881

    Google Scholar 

  12. Hoffman R, Silverstein MN (1991) Primary thrombocythemia. In: Hoffman R, Bentz EJ jr, Shattil SJ, Furie B, Cohen HJ (eds) Hematology, basic principles and practice. Churchill Livingstone, New York, pp 881–889

    Google Scholar 

  13. Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Hamaoka T, Paul WE (1982) Identification of a T-cell-derived B-cell growth factor distinct from interleukin-2. J Exp Med 155:914–923

    PubMed  Google Scholar 

  14. Imai Y, Tohda S, Nagata K, Suzuki T, Nara N, Aoki N (1991) Effects of recombinant interleukin-4 on the growth and differentiation of blast progenitors stimulated with G-CSF, GM-CSF and IL-3 from acute myeloblastic leukaemia patients. Br J Haematol 78:173–178

    PubMed  Google Scholar 

  15. Jansen JH, Fibbe WE, Wientjens GJHM, Willemze R, Kluin-Nelemans JC (1993) Inhibitory effect of interleukin-4 on the proliferation of acute myeloid leukemia cells with myelomonocytic differentiation (AML-M4/M5); the role of interleukin-6. Leukemia 7:643–645

    PubMed  Google Scholar 

  16. Jansen JH, Wientjens GJHM, Fibbe WE, Willemze R, Kluin-Nelemans JC (1989) Inhibition of human macrophage colony formation by interleukin-4. J Exp Med 170:577–582

    PubMed  Google Scholar 

  17. Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, McNiece IK, Jacobsen FW, Mendiaz EA, Birkett NC, Smith KA, Johnson MJ, Parker VP, Flores JC, Patel AC, Fisher EF, Erjavec HO, Herrera CJ, Wypych J, Sachdev RK, Pope JA, Leslie I, Wen D, Lin CH, Cupples RL, Zsebo KM (1990) Primary structure and functional expression of rat and human stem cell factor DNAs. Cell 63:201–211

    Google Scholar 

  18. McNiece IK, Langley KE, Zsebo KM (1991) Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. Exp Hematol 19:226–231

    PubMed  Google Scholar 

  19. Metcalf D (1991) Lineage commitment of hemopoietic progenitor cells in developing blast cell colonies: influence of colony-stimulating factors. Proc Natl Acad Sci USA 88:11310–11314

    PubMed  Google Scholar 

  20. Miyauchi J, Clark SC, Tsunematsu Y, Shimizu K, Park JW, Ogawa T, Toyama K (1991) Interleukin-4 as a growth regulator of clonogenic cells in acute myelogenous leukemia in suspension culture. Leukemia 5:108–115

    PubMed  Google Scholar 

  21. Moore MAS (1991) Clinical implications of positive and negative hematopoietic stem cell regulators. Blood 78:1–19

    PubMed  Google Scholar 

  22. Peschel C, William EP, Ohara J, Green I (1987) Effects of B cell stimulatory factor/interleukin-4 on hematopoietic progenitor cells. Blood 70:254–263

    PubMed  Google Scholar 

  23. Rennick D, Yang G, Muller-Sieburg C, Smith C, Arai N, Takabe Y, Gemmell L (1987) Interleukin 4 (B-cell stimulatory factor 1) can enchance or antagonize the factor-dependent growth of hematopoietic progenitor cells. Proc Natl Acad Sci USA 84:6889–6893

    PubMed  Google Scholar 

  24. Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293

    PubMed  Google Scholar 

  25. Sato N, Sawada K-I, Tarumi T, Koizumi K, Yasukouchi T, Takahashi TA, Sekiguchi S, Koike T (1994) Recombinant human interleukin-4 inhibits the production of granulocyte-macrophage colony-stimulating factor by blood mononuclear cells. Br J Haematol 86:695–701

    PubMed  Google Scholar 

  26. Sillaber C, Strobl H, Bevec D, Ashman LK, Butterfield JH, Lechner K, Maurer D, Bettelheim P, Valent P (1991) IL-4 regulates c-kit proto-oncogene product expression in human mast and myeloid progenitor cells. J Immunol 147:4224–4228

    PubMed  Google Scholar 

  27. Snoeck HW, Lardon F, Van Bockstaele DR, Peetermans ME (1993) Effects of interleukin-4 (IL 4) on myelopoiesis: studies on highly purified CD34+ hematopoietic progenitor cells. Leukemia 7:625–629

    PubMed  Google Scholar 

  28. Sonada Y, Okuda T, Yokota S, Maekawa T, Shizumi Y, Nishigaki H, Misawa S, Fujii H, Abe T (1990) Actions of human interleukin-4/B-cell stimulatory factor-1 on proliferation and differentiation of enriched hematopoietic progenitor cells in culture. Blood 75:1615–1621

    PubMed  Google Scholar 

  29. Te Velde AA, Klomp JPG, Yard BA, De Varies JE, Figdor CG (1988) Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol 140:1548–1554

    PubMed  Google Scholar 

  30. Tsuji K, Zsebo KM, Ogawa M (1991) Enhancement of murine blast cell colony formation in culture by recombinant rat stem cell factor, ligand for c-kit. Blood 78:1223–1229

    PubMed  Google Scholar 

  31. Vellenga E, de Wolf JTM, Beentjes JAM, Esselink MT, Smit JW, Halie MR (1990) Divergent effects of interleukin-4 (IL-4) on the granulocyte colony-stimulating factor and IL-3-supported myeloid colony formation from normal and leukemic bone marrow cells. Blood 75:633–637

    PubMed  Google Scholar 

  32. Wasserman LR (1971) The management of polycythaemia vera. Br J Haematol 21:371–376

    PubMed  Google Scholar 

  33. Welham MJ, Schrader JW (1991) Modulation of c-kit mRNA and protein by hemopoietic growth factors. Mol Cell Biol 11:2901–2904

    PubMed  Google Scholar 

  34. Wieser M, Bonifer R, Osler W, Lindemann A, Mertelsmann R, Herrmann F (1989) Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes. Blood 73:1105–1108

    PubMed  Google Scholar 

  35. Yokata T, Otsuka T, Mosmann T (1986) Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell and T-cell stimulating activities. Proc Natl Acad Sci USA 83:5894–5898

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of Oulu, Kajaanintie 50, FIN-90220, Oulu, Finland

    T. Siitonen, A. Zheng & P. Koistinen

  2. Department of Clinical Chemistry, University of Oulu, Finland

    E. -R. Savolainen

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  1. T. Siitonen
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  2. A. Zheng
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  3. E. -R. Savolainen
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  4. P. Koistinen
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Siitonen, T., Zheng, A., Savolainen, E.R. et al. The effect of interleukin-4 with or without mast cell growth factor on peripheral blood granulocyte-macrophage colony-forming cells in healthy controls and in myeloproliferative disorders. Ann Hematol 70, 203–207 (1995). https://doi.org/10.1007/BF01700376

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  • DOI: https://doi.org/10.1007/BF01700376

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