Andrews R G, Bartelmez S H, Knitter G H, Myerson D, Bernstein I D, Appelbaum F R, Zsebo K M
Pediatric Oncology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1992 Aug 15;80(4):920-7.
The ligand for the human c-kit, recombinant human stem cell factor (SCF), was administered to baboons at doses of 200, 100, 50, 25, and 10 micrograms/kg/d. SCF induced a dose-dependent expansion of hematopoietic colony-forming cells (CFC) of multiple types in both blood and marrow, including colony-forming unit (CFU) granulocyte-monocyte, burst-forming unit-erythroid, CFU-MIX, and high proliferative potential-CFC. These changes were associated with a dose-dependent leukocytosis, involving all leukocyte lineages, a reticulocytosis, and increases in marrow cellularity. At 200 micrograms/kg/d of SCF, CFC in blood were increased 10-fold to greater than 100-fold. This correlated with an increased frequency of CD34+ cells in blood. The frequency of CFC in blood approached that of marrow in some animals. These changes were reversed within 7 to 14 days of stopping SCF. The results of these studies suggest a role for the c-kit ligand in stimulating the expansion of multiple CFC types in blood and marrow for potential therapeutic purposes.
将重组人干细胞因子(SCF)作为人c-kit的配体,以200、100、50、25和10微克/千克/天的剂量给予狒狒。SCF诱导血液和骨髓中多种类型的造血集落形成细胞(CFC)呈剂量依赖性扩增,包括粒细胞-单核细胞集落形成单位(CFU)、红系爆式集落形成单位、CFU-MIX和高增殖潜能集落形成细胞。这些变化与剂量依赖性白细胞增多相关,涉及所有白细胞谱系、网织红细胞增多以及骨髓细胞增多。在SCF剂量为200微克/千克/天时,血液中的CFC增加了10倍至超过100倍。这与血液中CD34+细胞频率增加相关。在一些动物中,血液中CFC的频率接近骨髓中的频率。在停止使用SCF后7至14天内,这些变化逆转。这些研究结果表明,c-kit配体在刺激血液和骨髓中多种CFC类型扩增方面具有潜在治疗作用。