Cellular Immunology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
Cancer Immunol Immunother. 2010 Jun;59(6):885-97. doi: 10.1007/s00262-009-0815-3. Epub 2010 Feb 6.
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.
骨髓髓毒性是化疗的主要限制因素。虽然粒细胞集落刺激因子（G-CSF）治疗有效，但仍在寻求其他支持造血恢复的方法。我们之前发现，从灰树花（Grifola frondosa）中提取的β-葡聚糖提取物（MBG）增强了小鼠骨髓和人造血祖细胞（HPC）的集落形成单位-粒细胞单核细胞（CFU-GM）活性，刺激了 G-CSF 的产生，并使 HPC 免受阿霉素在体外的毒性。本研究评估了 MBG 在正常小鼠接受高剂量紫杉醇（Ptx）后对白细胞恢复和粒细胞/单核细胞功能的影响。在 B6D2F1 小鼠中给予累积剂量的 Ptx（90-120mg/kg）后，比较了每日口服 MBG（4 或 6mg/kg）、静脉内 G-CSF（80μg/kg）或 Ptx 单独使用对血液中白细胞恢复动力学、骨髓和脾脏 CFU-GM 活性以及粒细胞/单核细胞产生活性氧物质（ROS）的影响。与 Ptx 单独治疗（p=0.031）或 Ptx+G-CSF 治疗（p=0.024）相比，Ptx+MBG 小鼠的白细胞计数下降幅度较小。与 Ptx 单独治疗相比，Ptx+MBG 治疗后淋巴细胞水平更高（p<0.01）。MBG 在 Ptx 后 2 天增加了骨髓和脾脏中的 CFU-GM 活性（p<0.001，p=0.002）。在另外两天后（Ptx 后第 4 天），与 Ptx 单独治疗相比，MBG 使粒细胞/单核细胞 ROS 反应恢复到正常水平，并与 Ptx 单独治疗或 Ptx+G-CSF 治疗相比，增加了 ROS 反应（p<0.01，均）。这些研究表明，口服 MBG 促进了 HPC 的成熟，使其成为具有功能活性的髓样细胞，并增强了化疗性骨髓损伤后外周血白细胞的恢复。
