[#2010-12] Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity, Hong Lin et al.

Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity

Hong Lin • Elisa de Stanchina • Xi Kathy Zhou • Feng Hong • Andrew Seidman • Monica Fornier • Wei-Lie Xiao • Edward J. Kennelly • Kathleen Wesa • Barrie R. Cassileth • Susanna Cunningham-Rundles

Maitake

Abstract 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 B6D2Fl mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 p.g/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.