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. 1989 Apr;83(4):1308–1312. doi: 10.1172/JCI114016

Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes.

A Lindemann 1, D Riedel 1, W Oster 1, H W Ziegler-Heitbrock 1, R Mertelsmann 1, F Herrmann 1
PMCID: PMC303822  PMID: 2467922

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-alpha (TNF-alpha); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-alpha, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous signals, preferentially provided by the T cell-derived lymphokine GM-CSF. Stimulation of hematopoiesis and amplification of defense mechanisms after T cell activation thus might involve not only monocytes but also PMN, a cell type previously believed to be biosynthetically inactive.

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Selected References

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

  1. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Collart M. A., Belin D., Vassalli J. D., de Kossodo S., Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. doi: 10.1084/jem.164.6.2113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Donahue R. E., Wang E. A., Stone D. K., Kamen R., Wong G. G., Sehgal P. K., Nathan D. G., Clark S. C. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. 1986 Jun 26-Jul 2Nature. 321(6073):872–875. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
  5. Feinman R., Henriksen-DeStefano D., Tsujimoto M., Vilcek J. Tumor necrosis factor is an important mediator of tumor cell killing by human monocytes. J Immunol. 1987 Jan 15;138(2):635–640. [PubMed] [Google Scholar]
  6. Gasson J. C., Weisbart R. H., Kaufman S. E., Clark S. C., Hewick R. M., Wong G. G., Golde D. W. Purified human granulocyte-macrophage colony-stimulating factor: direct action on neutrophils. Science. 1984 Dec 14;226(4680):1339–1342. doi: 10.1126/science.6390681. [DOI] [PubMed] [Google Scholar]
  7. Grabstein K. H., Urdal D. L., Tushinski R. J., Mochizuki D. Y., Price V. L., Cantrell M. A., Gillis S., Conlon P. J. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science. 1986 Apr 25;232(4749):506–508. doi: 10.1126/science.3083507. [DOI] [PubMed] [Google Scholar]
  8. Granelli-Piperno A., Vassalli J. D., Reich E. Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other effectors. J Exp Med. 1977 Dec 1;146(6):1693–1706. doi: 10.1084/jem.146.6.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Griffin J. D., Ritz J., Nadler L. M., Schlossman S. F. Expression of myeloid differentiation antigens on normal and malignant myeloid cells. J Clin Invest. 1981 Oct;68(4):932–941. doi: 10.1172/JCI110348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heidorn K., Kreipe H., Radzun H. J., Müller R., Parwaresch M. R. The protooncogene c-fos is transcriptionally active in normal human granulocytes. Blood. 1987 Aug;70(2):456–459. [PubMed] [Google Scholar]
  11. Heisterkamp N., Groffen J., Stephenson J. R. Isolation of v-fms and its human cellular homolog. Virology. 1983 Apr 15;126(1):248–258. doi: 10.1016/0042-6822(83)90476-2. [DOI] [PubMed] [Google Scholar]
  12. Horiguchi J., Warren M. K., Kufe D. Expression of the macrophage-specific colony-stimulating factor in human monocytes treated with granulocyte-macrophage colony-stimulating factor. Blood. 1987 Apr;69(4):1259–1261. [PubMed] [Google Scholar]
  13. Hsiung H. M., Brousseau R., Michniewicz J., Narang S. A. Synthesis of human insulin gene. Part I. Development of reversed-phase chromatography in the modified triester method. Its application in the rapid and efficient synthesis of eight deoxyribooligonucleotides fragments constituting human insulin A DNA. Nucleic Acids Res. 1979 Apr;6(4):1371–1385. doi: 10.1093/nar/6.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huebner K., Isobe M., Croce C. M., Golde D. W., Kaufman S. E., Gasson J. C. The human gene encoding GM-CSF is at 5q21-q32, the chromosome region deleted in the 5q- anomaly. Science. 1985 Dec 13;230(4731):1282–1285. doi: 10.1126/science.2999978. [DOI] [PubMed] [Google Scholar]
  15. Ladner M. B., Martin G. A., Noble J. A., Nikoloff D. M., Tal R., Kawasaki E. S., White T. J. Human CSF-1: gene structure and alternative splicing of mRNA precursors. EMBO J. 1987 Sep;6(9):2693–2698. doi: 10.1002/j.1460-2075.1987.tb02561.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Levy P. C., Shaw G. M., LoBuglio A. F. Human monocyte, lymphocyte, and granulocyte antibody-dependent cell-mediated cytotoxicity toward tumor cells. I. General characteristics of cytolysis. J Immunol. 1979 Aug;123(2):594–599. [PubMed] [Google Scholar]
  17. Lindemann A., Riedel D., Oster W., Meuer S. C., Blohm D., Mertelsmann R. H., Herrmann F. Granulocyte/macrophage colony-stimulating factor induces interleukin 1 production by human polymorphonuclear neutrophils. J Immunol. 1988 Feb 1;140(3):837–839. [PubMed] [Google Scholar]
  18. Lopez A. F., Williamson D. J., Gamble J. R., Begley C. G., Harlan J. M., Klebanoff S. J., Waltersdorph A., Wong G., Clark S. C., Vadas M. A. Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. J Clin Invest. 1986 Nov;78(5):1220–1228. doi: 10.1172/JCI112705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  20. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
  21. Meuer S. C., Meyer zum Büschenfelde K. H. T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to T cell proliferation. J Immunol. 1986 Jun 1;136(11):4106–4112. [PubMed] [Google Scholar]
  22. Nedwin G. E., Svedersky L. P., Bringman T. S., Palladino M. A., Jr, Goeddel D. V. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1985 Oct;135(4):2492–2497. [PubMed] [Google Scholar]
  23. Oster W., Lindemann A., Ganser A., Mertelsmann R., Herrmann F. Constitutive expression of hematopoietic growth factor genes by acute myeloblastic leukemia cells. Behring Inst Mitt. 1988 Aug;(83):68–79. [PubMed] [Google Scholar]
  24. Sariban E., Mitchell T., Kufe D. Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature. 1985 Jul 4;316(6023):64–66. doi: 10.1038/316064a0. [DOI] [PubMed] [Google Scholar]
  25. Schwartz R. J., Haron J. A., Rothblum K. N., Dugaiczyk A. Regulation of muscle differentiation: cloning of sequences from alpha-actin messenger ribonucleic acid. Biochemistry. 1980 Dec 9;19(25):5883–5890. doi: 10.1021/bi00566a034. [DOI] [PubMed] [Google Scholar]
  26. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  27. Taylor J. L., Turo K. A., McCann P. P., Grossberg S. E. Inhibition of the differentiation of 3T3-L1 cells by interferon-beta and difluoromethyl ornithine. J Biol Regul Homeost Agents. 1988 Jan-Mar;2(1):19–24. [PubMed] [Google Scholar]
  28. Tiku K., Tiku M. L., Liu S., Skosey J. L. Normal human neutrophils are a source of a specific interleukin 1 inhibitor. J Immunol. 1986 May 15;136(10):3686–3692. [PubMed] [Google Scholar]
  29. Tushinski R. J., Oliver I. T., Guilbert L. J., Tynan P. W., Warner J. R., Stanley E. R. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982 Jan;28(1):71–81. doi: 10.1016/0092-8674(82)90376-2. [DOI] [PubMed] [Google Scholar]
  30. Warren M. K., Ralph P. Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity. J Immunol. 1986 Oct 1;137(7):2281–2285. [PubMed] [Google Scholar]
  31. Weisbart R. H., Golde D. W., Clark S. C., Wong G. G., Gasson J. C. Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator. 1985 Mar 28-Apr 3Nature. 314(6009):361–363. doi: 10.1038/314361a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  34. Young D. C., Wagner K., Griffin J. D. Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia. J Clin Invest. 1987 Jan;79(1):100–106. doi: 10.1172/JCI112769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ziegler-Heitbrock H. W., Riethmüller G. A rapid assay for cytotoxicity of unstimulated human monocytes. J Natl Cancer Inst. 1984 Jan;72(1):23–29. doi: 10.1093/jnci/72.1.23. [DOI] [PubMed] [Google Scholar]

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