Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity.
Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90-120 mg/kg) given to B6D2F1mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 microg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury.
Cellular Immunology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
Hong
H
Lin
Elisa
E
de Stanchina
Xi Kathy
XK
Zhou
Feng
F
Hong
Andrew
A
Seidman
Monica
M
Fornier
Wei-Lie
WL
Xiao
Edward J
EJ
Kennelly
Kathleen
K
Wesa
Barrie R
BR
Cassileth
Susanna
S
Cunningham-Rundles
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D055014:Granulocyte-Macrophage Progenitor Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D048691:Grifola; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019891:Leukopoiesis / Q000187:drug effects; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D047071:beta-Glucans / Q000008:administration & dosage*
D004040:Dietary Carbohydrates; D017382:Reactive Oxygen Species; D047071:beta-Glucans; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017239:Paclitaxel