Efficient mobilization of haematopoietic progenitors after a single injection of pegylated recombinant human granulocyte colony-stimulating factor in mouse strains with distinct marrow-cell pool sizes
Efficient mobilization of haematopoietic progenitors after a single injection of pegylated recombinant human granulocyte colony-stimulating factor in mouse strains with distinct marrow-cell pool sizes
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DOI：
10.1046/j.1365-2141.2000.02252.x
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发表时间：
2000-09-01
影响因子：
6.5
通讯作者：
Dontje, B
中科院分区：
文献类型：
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作者：
de Haan, G;Ausema, A;Dontje, B
我们比较了单次注射 SD/01（一种新设计的聚乙二醇化形式的重组人粒细胞集落刺激因子 (rhG-CSF)）与单次注射糖基化 rhG-CSF（非格司亭）的功效。 SD/01 给予常规和重组近交系小鼠（AKR、C557L/J、DBA/2、C57BL/6、AKXL），已知这些小鼠具有广泛不同的骨髓细胞池大小和增殖动力学。单次注射 G-CSF 无法动员粒细胞-巨噬细胞集落形成单位 (CFU-GM)。与此形成鲜明对比的是，单剂量的 SD/01 导致祖细胞和干细胞的大量动员。尽管所有小鼠品系都表现出相似的动员反应，但品系间仍存在较大差异。 C57L 和 C57BL/6 小鼠的活动能力相对较差，而 AKR 和 DBA/2 小鼠则表现出三倍到十倍的优异反应。为了解释这些不同的表型，我们研究了 SD/01 在九个 AKXL 重组近交系中的影响，这些近交系源自反应良好的 AKR 和反应较差的 C57L 亲本品系。这些菌株中 SD/01 反应性的最佳预测因子是动员前的骨髓细胞结构。将 AKXL 菌株的骨髓细胞分布模式与先前在这些菌株中定位的基因座进行比较，结果显示与 Ant 完全一致，Ant 是一种映射到 12 号染色体的丝氨酸蛋白酶抑制剂。
We have compared the efficacy of a single injection of SD/01, a newly engineered, pegylated form of recombinant human granulocyte colony stimulating factor (rhG-CSF), with a single injection of glycosylated rhG-CSF (Filgrastim). SD/01 was administered to regular and recombinant inbred strains of mice (AKR, C557L/J, DBA/2, C57BL/6, AKXL) known to have widely distinct marrow-cell pool sizes and proliferation kinetics. A single injection of G-CSF was unable to mobilize granulocyte-macrophage colony-forming units (CFU-GM). In sharp contrast, a single dose of SD/01 resulted in massive mobilization of progenitors and stem cells. Although all mice strains showed qualitatively similar mobilization responses, large interstrain differences remained. C57L and C57BL/6 mice mobilized relatively poorly, whereas AKR and DBA/2, mice showed threefold to tenfold superior responses, In order to explain these different phenotypes, we studied the effects of SD/01 in nine AKXL recombinant inbred strains, derived from well-responding AKR and poorly responding C57L parental strains. The best predictor for SD/01 responsiveness in these strains was marrow cellularity prior to mobilization. Comparison of the AKXL strain distribution pattern for marrow cellularity with loci previously mapped in these strains showed complete concordance with Ant, a serine protease inhibitor mapping to chromosome 12.