Patchen M L, Liang J, Vaudrain T, Martin T, Melican D, Zhong S, Stewart M, Quesenberry P J
Alpha-Beta Technology, Inc., Worcester, Massachusetts 01605, USA.
Stem Cells. 1998;16(3):208-17. doi: 10.1002/stem.160208.
Betafectin PGG-Glucan, a novel beta-(1,6) branched beta-(1,3) glucan purified from the cell walls of Saccharomyces cerevisiae, has been shown to synergize with myeloid growth factors in vitro and to enhance hematopoietic recovery in myelosuppressed mice and primates. Here we report that PGG-Glucan is also capable of mobilizing peripheral blood progenitor cells (PBPC). PGG-Glucan (0.5 mg/kg to 16 mg/kg) was administered intravenously to C3H/HeN male mice and blood collected at times ranging from 30 min to seven days after injection. Based on granulocyte-macrophage colony-forming cell (GM-CFC) levels, peak mobilization occurred 30 min after a 2 mg/kg PGG-Glucan dose. At this time GM-CFC numbers in PGG-Glucan-treated mice were approximately fourfold greater than in saline-treated control mice. A second, smaller wave of GM-CFC mobilization (approximately twofold increase) also occurred on days 4 and 5 after PGG-Glucan treatment. Mobilization was not associated with the induction of alpha-chemokines, which have recently been reported to induce rapid progenitor cell mobilization. Competitive repopulation experiments performed in irradiated female C3H/HeN mice revealed that, at three months after transplantation, more male DNA was present in bone marrow, splenic, and thymic tissues from animals transplanted with cells obtained from mice 30 min after a 2 mg/kg PGG-Glucan dose than in tissues from animals transplanted with cells obtained from saline-treated mice. Additional experiments evaluated the mobilization effects of PGG-Glucan (2 mg/kg) administered to mice which had been pretreated for three consecutive days with G-CSF (125 microg/kg/day). When blood was collected 30 min after PGG-Glucan treatment, the number of GM-CFC mobilized in combination-treated mice was additive between the number mobilized in mice treated with G-CSF alone and the number mobilized in mice treated with PGG-Glucan alone. These studies demonstrate that: A) PGG-Glucan can rapidly mobilize PBPC; B) the kinetic pattern of PGG-Glucan-induced mobilization is different from that of the CSFs; C) the reconstitutional potential of PGG-Glucan mobilized cells is greater than that of steady-state PBPC, and D) PGG-Glucan can enhance G-CSF-mediated PBPC mobilization.
β-葡聚糖（Betafectin PGG-Glucan）是一种从酿酒酵母细胞壁中纯化得到的新型β-(1,6)分支β-(1,3)葡聚糖，已证实在体外它能与髓系生长因子协同作用，并能促进骨髓抑制小鼠和灵长类动物的造血恢复。在此我们报告PGG-葡聚糖还能够动员外周血祖细胞（PBPC）。将PGG-葡聚糖（0.5毫克/千克至16毫克/千克）静脉注射给C3H/HeN雄性小鼠，并在注射后30分钟至7天的不同时间采集血液。基于粒细胞-巨噬细胞集落形成细胞（GM-CFC）水平，在给予2毫克/千克PGG-葡聚糖剂量后30分钟出现峰值动员。此时，PGG-葡聚糖处理小鼠的GM-CFC数量比生理盐水处理的对照小鼠大约多四倍。在PGG-葡聚糖处理后的第4天和第5天还出现了第二次较小的GM-CFC动员波（大约增加两倍）。动员与α-趋化因子的诱导无关，最近有报道称α-趋化因子可诱导祖细胞快速动员。在经辐照的雌性C3H/HeN小鼠中进行的竞争性再增殖实验表明，移植后三个月，与移植用生理盐水处理小鼠的细胞所获得的组织相比，移植用2毫克/千克PGG-葡聚糖剂量后30分钟从小鼠获得的细胞所移植的动物的骨髓、脾脏和胸腺组织中存在更多的雄性DNA。其他实验评估了给连续三天用G-CSF（125微克/千克/天）预处理的小鼠施用PGG-葡聚糖（2毫克/千克）的动员效果。在PGG-葡聚糖处理后30分钟采集血液时，联合处理小鼠中动员的GM-CFC数量是单独用G-CSF处理的小鼠中动员的数量与单独用PGG-葡聚糖处理的小鼠中动员的数量之和。这些研究表明：A）PGG-葡聚糖能快速动员PBPC；B）PGG-葡聚糖诱导动员的动力学模式与集落刺激因子（CSF）不同；C）PGG-葡聚糖动员的细胞的重建潜力大于稳态PBPC；D）PGG-葡聚糖能增强G-CSF介导的PBPC动员。
