Migliaccio A R, Migliaccio G, Dale D C, Hammond W P
Division of Hematology, University of Washington, Seattle.
Blood. 1990 May 15;75(10):1951-9.
The number and growth factor requirements of committed progenitor cells (colony-forming units-granulocyte/macrophage and burst-forming units-erythroid) in three patients with cyclic neutropenia (two congenital, one acquired) were studied before and during therapy with recombinant human granulocyte colony-stimulating factor (G-CSF; 3 to 10 micrograms/kg/d). When the patients with congenital disease were treated with G-CSF, the cycling of blood cells persisted, but the cycle length was shortened from 21 days to 14 days, and the amplitude of variations in blood counts increased. There was a parallel shortening of the cycle and increase of the amplitude of variations (from two- to three-fold to 10- to 100-fold) in the number of both types of circulating progenitor cells in these two patients. In the patient with acquired cyclic neutropenia, cycling of both blood cells and progenitors could not be seen. In cultures deprived of fetal bovine serum, erythroid and myeloid bone marrow progenitor cells from untreated patients and from normals differed in growth factor responsiveness. As examples, maximal growth of granulocyte/macrophage (GM) colonies was induced by granulocyte/macrophage (GM)-CSF plus G-CSF in the patients, whereas a combination of GM-CSF, G-CSF and interleukin-3 (IL-3) was required in the normals, and erythropoietin alone induced fourfold more erythroid bursts from cyclic neutropenic patients than from normal donors (46% versus 11% of the maximal colony number, respectively). The growth factor responsiveness of marrow progenitor cells slightly changed during the treatment toward the values observed with normal progenitors. These results indicate that treatment with G-CSF not only ameliorated the neutropenia, but also increased the amplitude and the frequency of oscillation of circulating progenitor cell numbers. These data are consistent with the hypothesis that G-CSF therapy affects the proliferation of the hematopoietic stem cell.
研究了3例周期性中性粒细胞减少症患者（2例先天性，1例后天性）在接受重组人粒细胞集落刺激因子（G-CSF；3至10微克/千克/天）治疗之前和治疗期间定向祖细胞（集落形成单位-粒细胞/巨噬细胞和爆式红系集落形成单位）的数量及生长因子需求。先天性疾病患者接受G-CSF治疗时，血细胞的循环持续存在，但周期长度从21天缩短至14天，血细胞计数的变化幅度增加。这两名患者中两种循环祖细胞的数量均出现了周期平行缩短以及变化幅度增加（从2至3倍增至10至100倍）的情况。在后天性周期性中性粒细胞减少症患者中，未观察到血细胞和祖细胞的循环现象。在不含胎牛血清的培养物中，未经治疗的患者和正常人的红系和髓系骨髓祖细胞对生长因子的反应性有所不同。例如，患者的粒细胞/巨噬细胞（GM）集落最大生长由粒细胞/巨噬细胞（GM）-CSF加G-CSF诱导，而正常人则需要GM-CSF、G-CSF和白细胞介素-3（IL-3）的联合作用，并且单独使用促红细胞生成素时，周期性中性粒细胞减少症患者产生的红系爆式集落比正常供体多四倍（分别为最大集落数的46%和11%）。骨髓祖细胞的生长因子反应性在治疗期间略有变化，趋向于正常祖细胞所观察到的值。这些结果表明，G-CSF治疗不仅改善了中性粒细胞减少症，还增加了循环祖细胞数量的振荡幅度和频率。这些数据与G-CSF治疗影响造血干细胞增殖的假说一致。
