Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Interleukin-9 stimulates the proliferation of enriched human erythroid progenitor cells: additive effect with GM-CSF

  • 26 Accesses

  • 10 Citations

Summary

In the study we report here we investigated the colony-stimulating activities of interleukin-9 (IL-9). In the presence of erythropoietin, IL-9 was found to stimulate the proliferation of relatively early erythroid progenitor cells (BFU-E) from normal human bone marrow cells depleted of mononuclear phagocytes and T lymphocytes. Neutralization experiments demonstrated that the observed BFU-E-stimulating effect was not the result of intermediate production of IL-3 or GM-CSF by residual accessory cells in response to IL-9. Accordingly, the effects of IL-9 were preserved when cell suspensions were further depleted of accessory cells using CD34 enrichment of progenitor cells. Furthermore, IL-9 did not stimulate bone marrow mononuclear cells to express mRNA for IL-3, GM-CSF, EPA (erythroid-promoting activity), or IL-4, as determined by a cDNA-PCR method. IL-9 is likely to act on a subpopulation of IL-3-responsive erythroid progenitor cells that are not stimulated by GM-CSF, since plateau concentration of IL-9 and GM-CSF had additive effects on BFU-E formation, whereas a combination of IL-9 and IL-3 did not. In addition to its burst-promoting activity, IL-9 was found to have a modest stimulatory activity on myeloid progenitor cells (CFU-GM) in some experiments, suggesting that this effect may be donor related.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Brown CB, Hart CE, Curtis DM, Baily MC, Kaushansky K (1990) Two neutralizing monoclonal antibodies against human granulocyte-macrophage colony-stimulating factor recognize the receptor binding domain of the molecule. J Immunol 144: 2184

  2. 2.

    Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt Biochem 162: 156

  3. 3.

    Donahue RE, Yang Y-C, Clark SC (1990) Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation. Blood 75: 2271

  4. 4.

    Druez C, Coulie P, Uyttenhove C, Van Snick J (1990) Functional and biochemical characterization of mouse P40/IL-9 receptors. J Immunol 145: 2494

  5. 5.

    Fauser AA, Messner HA (1979) Idenitication of megakaryocytes, macrohphages and eosinophils in colonies of human bone marrow containing neutrophilic granulocytes and erythroblasts. Blood 53: 1023

  6. 6.

    Fraser JK, Lin FK, Berridge MV (1988) Expression and modulation of specific high-affinity binding sites for erythropoietin on the human erythroleukemic cell line K562. Blood 71: 104

  7. 7.

    Hultner L, Druez C, Moeller J, Uyttenhove C, Schmitt E, Rude E, Dormer P, Van Snick J (1990) Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse. T-cell growth factor P40/TCGFIII (interleukin 9). Eur J Immunol 20: 1413

  8. 8.

    Kaashoek JGJ, Mout R, Falkenburg JHF, Willemze R, Fibbe WE, Landegent JE (1991) Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. Cytokine Lymphokine Res 10: 231

  9. 9.

    Mitjavila MT, Natazawa M, Brignaschi P, Debili N, Breton-Gorius J, Vainchenker W (1989) Effects of five recombinant hematopoietic growth factors on enriched human erythroid progenitors in serum-replaced cultures. J Cell Physiol 138: 617

  10. 10.

    Peschel C, Paul WE, Ohara J, Green I (1978) Effects of B-cell stimulatory factor-1/interleukin-4 on hematopoietic progenitor cells. Blood 70: 254

  11. 11.

    Renauld J-C, Goethals A, Houssiau F, Van Roost E, Van Snick J (1990) Cloning and expression of a cDNA for the human homolog of mouse T cell and must cell growth factor P40. Cytokine 2: 9

  12. 12.

    Renauld J-C, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J (1990) Human P40/interleukin-9: expression in activated CD 4+ T cells, genomic organization and comparison with the mouse gene. J Immunol 144: 4235

  13. 13.

    Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239: 487

  14. 14.

    Schaafsma MR, Falkenburg JHF, Duinkerken N, Van Damme J, Altrock BW, Willemze R, Fibbe WE (1989) Interleukin-1 synergizes with granulocyte-macrophage colony-stimulating factor on granulocytic colony formation by intermediate production of granulocyte colony-stimulating factor. Blood 74: 2398

  15. 15.

    Schmitt E, Van Brandwijk R, Van Snick J, Siebold B, Rude E (1989) TCGFIII/P40 is produced by naive murine CD4+ T cells but is not a general T-cell growth factor. Eur J Immunol 19: 2167

  16. 16.

    Snick J Van, Goethals A, Renauld J-C, Van Roost E, Uyttenhove C, Rubira MR, Moritz RL, Simpson RJ (1989) Cloning and characterization of a cDNA for a new mouse T-cell growth factor (P40). J Exp Med 169: 363

  17. 17.

    Sonoda Y, Yang Y-C, Wong GG, Clark SC, Ogawa M (1988) Erythroid burst-promoting activity of purified recombinant human GM-CSF and interleukin-3: studies with anti-GM-CSF and anti-IL-3 sera and studies in serum-free cultures. Blood 72: 1381

  18. 18.

    Strife A, Lambek C, Wisniewski D, Gulati S, Gasson JC, Golde DW, Welte K, Gabrilove JL, Clarkson B (1987) Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells. Blood 69: 1508

  19. 19.

    Uyttenhove C, Simpson RJ, Van Snick J (1988) Functional and structural characterization of P 40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci USA 85: 6934

  20. 20.

    Uyttenhove C, Druez C, Renauld J-C, Herin M, Noel H, Van Snick J (1991) Autonomous growth and tumorigenicity induced by P40/interleukin-9 cDNA transfection of a mouse P40-dependent T-cell line. J Exp Med 173: 519

  21. 21.

    Westbrook CA, Gasson JC, Gerber SE, Selsted ME, Golde DW (1984) Purification and characterization of human T-lymphocyte-derived erythroid-potentiating activity. J Biol Chem 259: 9992

  22. 22.

    Williams DE, Morrissey PJ, Mochizuki DY, De Vries P, Anderson D, Cosman D, Boswell HC, Cooper S, Grabstein KH, Broxmeyer HE (1990) T-cell growth factor P40 promotes the proliferation of myeloid cell lines and enhances erythroid burst formation by normal murine bone marrow cells in vitro. Blood 76: 906

  23. 23.

    Yang Y-C, Ricciardi S, Ciarletta A, Calvetti J, Kelleher K, Clark SC (1989) Expression cloning of a cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40. Blood 74: 1880

Download references

Author information

Correspondence to M. R. Schaafsma.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schaafsma, M.R., Falkenburg, J.H.F., Duinkerken, N. et al. Interleukin-9 stimulates the proliferation of enriched human erythroid progenitor cells: additive effect with GM-CSF. Ann Hematol 66, 45–49 (1993). https://doi.org/10.1007/BF01737688

Download citation

Key words

  • Interleukin-9
  • BFU-E