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Vol. 102, No. 2, 1999
Issue release date: October 1999

The Polysaccharide, PGG-Glucan, Enhances Human Myelopoiesis by Direct Action Independent of and Additive to Early-Acting Cytokines

Turnbull J.L. · Patchen M.L. · Scadden D.T.
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Abstract

β-Glucans stimulate leukocyte anti-infective activity, enhance murine hematopoietic recovery following bone marrow injury and mobilize murine progenitor cells from bone marrow. This study evaluated the in vitro hematopoietic potential of the β-glucan, PGG-glucan, on human bone marrow mononuclear cells (BMMC) and CD34+ BMMC compared with protein cytokines. In the presence of submaximal concentrations of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 0.5 ng/ml), PGG-glucan significantly increased BMMC myeloid colony formation comparable to the increase observed with either interleukin-3 (rhIL-3) or stem cell factor (rhSCF). Moreover, the addition of PGG-glucan to cultures containing GM-CSF + IL-3 or GM-CSF + SCF significantly augmented granulocyte-macrophage colony production above baseline, demonstrating that PGG-glucan acts independently of those early-acting cytokines and can enhance their activity in an additive manner. Anti-PGG-glucan monoclonal antibody specifically abrogated the growth-enhancing effect of added PGG-glucan in a saturable manner and other control carbohydrate polymers failed to affect colony formation. Further, PGG-glucan was not associated with induction of IL-6, GM-CSF production and removal of accessory cells by CD34+ cell isolation did not alter the PGG-glucan effect. These data demonstrate that PGG-glucan acts on committed myeloid progenitors to enhance human hematopoietic activity by a mechanism of direct action independent of IL-3 or SCF and independent of secondary cytokine stimulation.



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References

  1. DiLuzio NR, McNamee R, Browder WI, Williams D: Inhibition of tumor growth and enhancement of survival in four syngeneic murine tumor models. Cancer Treat Rep 1978;62:1857–1866.

    External Resources

  2. Mansell PWA, DiLuzio NR, McNamee R, Rowden G, Proctor JW: Recognition factors and nonspecific macrophage activation in the treatment of neoplastic disease. Ann NY Acad Sci 1976;277:20–44.

    External Resources

  3. Mansell PW, Ichinose H, Reed RJ, Krementa ET, McNamee R, DiLuzio NR: Macrophage mediated destruction of human malignant cells in vivo. J Natl Cancer Inst 1975;54:571–580.

    External Resources

  4. Williams DL, Sherwood ER, Browder W, McNamee RB, Jones EL, Rakinic J, Di Luzio NR: Effect of glucan on neutrophil dynamics and immune function in Escherichia coli peritonitis. J Surg Res 1988;44:54–61.
  5. DiLuzio NR, Williams DL, McNamee RB, Edwards BF, Kitahama A: Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan. Int J Cancer 1979;24:773–779.

    External Resources

  6. DiLuzio NR, Williams DL: Protective effect of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice. Infect Immun 1978;20:804–810.

    External Resources

  7. Kokoshis PL, Williams DL, Cook JA, DiLuzio NR: Increased resistance to Staphylococcus aureus infection and enhancement in serum lysozyme activity by glucan. Science 1978;199:1340–1342.

    External Resources

  8. Burgaleta C, Territo MC, Quan SG, Golde DW: Glucan-activated macrophages: Functional characteristics and surface morphology. J Reticuloendothel Soc 1978;23:195–204.

    External Resources

  9. Burgaleta C, Golde DW: Effect of glucan on granulopoiesis and macrophage genesis in mice. Cancer Res 1977;37:1739–1742.

    External Resources

  10. Patchen ML, Lotzova E: Modulation of murine hemopoiesis by glucan. Exp Hematol 1980;8:409–422.

    External Resources

  11. Patchen ML, MacVittie TJ: Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan. Immunopharmacology 1983;5:303–313.
  12. Patchen ML, MacVittie TJ: Temporal response of murine pluripotent stem cells and myeloid and erythroid progenitor cells to low-dose glucan treatment. Acta Haematol 1983;70:281–288.

    External Resources

  13. Niskanen EO, Burgaleta C, Cline MJ, Golde DW: Effect of glucan, a macrophage activator, on murine hemopoietic cell proliferation in diffusion chambers in mice. Cancer Res 1978;38:1406–1409.

    External Resources

  14. Onderdonk AB, Cisneros RL, Hinkson P, Ostroff G: Anti-infective effect of poly-β1,3 glucopyranose glucan in vivo. Infect Immun 1992;60:1642–1647.
  15. Patchen ML, MacVittie TJ, Solberg BD, Souza LM: Survival enhancement and hematopoietic regeneration following radiation exposure: Therapeutic approach using glucan and granulocyte colony-stimulating factor. Exp Hematol 1990;18:1042–1048.
  16. Patchen ML, D’Alesandro MM, Brook I, Blakely WF, MacVittie TJ: Glucan: Mechanisms involved in its ‘radioprotective’ effect. J Leukoc Biol 1987;42:95–105.
  17. Patchen ML, Lotzova E: The role of macrophages and T-lymphocytes in glucan-mediated alteration of murine hemopoiesis. Biomedicine 1981;34:71–77.

    External Resources

  18. Babineau TJ, Hackford A, Kenler A, Bistrian B, Forse RA, Fairchild PG, et al: A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients. Arch Surg 1994;129:1204–1210.
  19. Babineau TJ, Marcello P, Swails W, Kenler A, Bistrain B, Forse RA: Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-glucan) in high-risk surgical patients. Ann Surg 1994;220:601–609.
  20. Bleicher P, Mackin W: Betafectin PGG-glucan: A novel carbohydrate immunomodulator with anti-infective properties. J Biotechnol Healthcare 1995;2/2:207–222.
  21. Patchen ML, Bleicher P, Liang J, Vaudrain T, Maschek BJ, Jackson JD: Mobilization of peripheral blood progenitor cells by Betafectin PGG-glucan. Exp Hematol 1996;24:1032.
  22. Lane RD: A short-duration polyethylene glycol fusion technique for increasing production of monoclonal antibody-secreting hybridomas. J Immunol 1985;81:223–228.
  23. Adams DS, Pero SC, Petro JD, Nathans R, Mackin WM, Wakshull E: PGG-glucan activates NF-kappaB-like and NF-IL-6-like transcription factor complexes in a murine monocytic cell line. J Leukoc Biol 1977;62:865–873.


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