Maitake beta-glucan enhances granulopoiesis and mobilization of granulocytes by increasing G-CSF production and modulating CXCR4/SDF-1 expression

Int Immunopharmacol. 2009 Sep;9(10):1189-96. doi: 10.1016/j.intimp.2009.06.007. Epub 2009 Jun 30.


Previous studies have presented that Maitake beta-glucan (MD-Fraction) extracted from the fruit body of Grifola frondosa has an anti-tumor effect by activating the immune system. Recently, the stimulating effects of beta-glucans on hematopoiesis were identified as new characteristics of polysaccharides, possibly helping to relieve the immunosuppression which results from chemotherapies. We demonstrated that the production of granulocyte colony-stimulating factor (G-CSF) was significantly enhanced by MD-Fraction (8mg/kg, i.p.) in granulocytopenic model induced in mice using cyclophosphamide (200mg/kg, i.p.). In addition, MD-Fraction induced a biphasic increase in the number of granulocytes in the spleen. The mechanism for the increase in granulocytes on the early phase on day 1 might involve the increased mRNA expression of macrophage inflammatory protein-2 (MIP-2), in the splenic cells, thereby recruiting granulocytes into the spleen. Interestingly, a decline of myeloid progenitors in the bone marrow and an increase in granulocytes in the peripheral blood were observed on day 5, suggesting a mobilization of granulocytes and their progenitors from the bone marrow to the peripheral blood. We confirmed that a possible mechanism in which MD-Fraction promoted the mobilization of granulocytes and their progenitors from the bone marrow is down-regulating the expression of the chemokine receptor, CXCR4, and its ligand, stromal cell-derived factor 1 (SDF-1) in the bone marrow microenvironment. These results reveal a novel function of Maitake beta-glucan that enhances the granulopoiesis and mobilization of granulocytes and their progenitors by stimulating G-CSF production. This finding presents opportunities to develop new therapeutic strategies against the immunosuppression caused by chemotherapies in cancer patients.

MeSH terms

  • Agranulocytosis / chemically induced
  • Agranulocytosis / drug therapy*
  • Agranulocytosis / pathology
  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / immunology
  • Chemokine CXCL12 / metabolism*
  • Chemokine CXCL2 / metabolism
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Drug-Related Side Effects and Adverse Reactions
  • Granulocyte Colony-Stimulating Factor / biosynthesis*
  • Granulocyte Colony-Stimulating Factor / blood
  • Granulocyte Colony-Stimulating Factor / genetics
  • Granulocyte Colony-Stimulating Factor / immunology
  • Granulocytes / drug effects*
  • Granulocytes / immunology
  • Granulocytes / metabolism
  • Granulocytes / pathology
  • Grifola*
  • Hematopoiesis / drug effects*
  • Hematopoiesis / immunology
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Male
  • Mice
  • Mice, Inbred C3H
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology


  • Chemokine CXCL12
  • Chemokine CXCL2
  • Cxcl12 protein, mouse
  • Immunosuppressive Agents
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide