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.
Lin
Hong
H
Cellular Immunology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
de Stanchina
Elisa
E
Zhou
Xi Kathy
XK
Hong
Feng
F
Seidman
Andrew
A
Fornier
Monica
M
Xiao
Wei-Lie
WL
Kennelly
Edward J
EJ
Wesa
Kathleen
K
Cassileth
Barrie R
BR
Cunningham-Rundles
Susanna
S
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