Lin Hong, Cheung Sandy W Y, Nesin Mirjana, Cassileth Barrie R, Cunningham-Rundles Susanna
Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Clin Vaccine Immunol. 2007 Jan;14(1):21-7. doi: 10.1128/CVI.00284-06. Epub 2006 Nov 8.
Maitake beta-glucan (MBG) is an extract from the fruit body of the Grifola frondosa mushroom that is being widely used to treat cancer in Asia. We have previously reported that MBG enhances mouse bone marrow cell (BMC) hematopoiesis in vitro and protects BMC from doxorubicin (DOX) toxicity. In the current study, we investigated the ability of MBG to enhance hematopoiesis and to reduce the toxic effects of DOX on fresh human umbilical cord blood (CB) cells. MBG treatment significantly enhanced the colony formation unit (CFU) response of granulocytes-macrophages (CFU-GM response) over the whole dose range of 12.5 to 100 microg/ml (P < 0.05). The addition of MBG to DOX-treated CB cells significantly protected granulocyte-macrophage colony formation from the toxicity of DOX, which otherwise produced strong hematopoietic repression. MBG also partially replaced recombinant human granulocyte colony-stimulating factor (rhG-CSF), as shown by a significant augmentation of the CFU-GM response in the absence of rhG-CSF. We found that MBG induces granulocyte colony-stimulating factor (G-CSF) production in CB CD33+ monocytes, as detected by intracellular cytokine flow cytometric assessment. In contrast, we found that adult peripheral blood monocytes did not produce a significant G-CSF response to MBG, whereas both adult and CB monocytes produced G-CSF in response to lipopolysaccharide. These studies provide the first evidence that MBG induces hematopoietic stem cell proliferation and differentiation of CFU-GM in umbilical CB cells and acts directly to induce G-CSF.
舞茸β-葡聚糖(MBG)是从云芝子实体中提取的物质,在亚洲被广泛用于治疗癌症。我们之前报道过,MBG在体外可增强小鼠骨髓细胞(BMC)的造血功能,并保护BMC免受阿霉素(DOX)的毒性影响。在本研究中,我们调查了MBG增强造血功能以及降低DOX对新鲜人脐带血(CB)细胞毒性作用的能力。在12.5至100微克/毫升的整个剂量范围内,MBG处理均显著增强了粒细胞-巨噬细胞集落形成单位(CFU)反应(CFU-GM反应)(P<0.05)。向经DOX处理的CB细胞中添加MBG可显著保护粒细胞-巨噬细胞集落形成免受DOX的毒性影响,否则DOX会产生强烈的造血抑制作用。MBG还部分替代了重组人粒细胞集落刺激因子(rhG-CSF),这表现为在无rhG-CSF的情况下CFU-GM反应显著增强。我们发现,通过细胞内细胞因子流式细胞术评估检测到,MBG可诱导CB CD33+单核细胞产生粒细胞集落刺激因子(G-CSF)。相比之下,我们发现成人外周血单核细胞对MBG未产生显著的G-CSF反应,而成人和CB单核细胞对脂多糖均产生G-CSF反应。这些研究提供了首个证据,即MBG可诱导脐带CB细胞中造血干细胞增殖和CFU-GM分化,并直接作用诱导G-CSF产生。