Maitake beta-glucan enhances granulopoiesis and mobilization of granulocytes by increasing G-CSF production and modulating CXCR4/SDF-1 expression.
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.
Ito
Koichi
K
Department of Microbial Chemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Japan. k.ito@griffith.edu.au
Masuda
Yuki
Y
Yamasaki
Yoshihiko
Y
Yokota
Yoshinobu
Y
Nanba
Hiroaki
H
D000380:Agranulocytosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D048691:Grifola; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology
D054377:Chemokine CXCL12; D054426:Chemokine CXCL2; C515256:Cxcl12 protein, mouse; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide