Schuening F G, Storb R, Goehle S, Nash R, Graham T C, Appelbaum F R, Hackman R, Sandmaier B M, Urdal D L
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Exp Hematol. 1989 Sep;17(8):889-94.
The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on canine hematopoiesis was evaluated. rhGM-CSF stimulated granulocyte-macrophage colony formation of canine marrow depleted of accessory cells up to tenfold. Stimulation of colony formation was abrogated by anti-rhGM-CSF antiserum or heat inactivation. rhGM-CSF also stimulated in vivo canine hematopoiesis both when given as continuous i.v. infusion and as intermittent s.c. injections. Neutrophil, monocyte, and lymphocyte counts were increased three- to eightfold above controls, whereas values for eosinophils, reticulocytes, and hematocrits were not changed. Bone marrow histology after 2 weeks of treatment with rhGM-CSF showed hypercellularity with myeloid hyperplasia and left-shifted granulocytopoiesis. After discontinuation of rhGM-CSF, peripheral leukocyte counts returned to control level within 3-7 days. Platelet counts decreased rapidly after starting rhGM-CSF, to 5000-15,000 platelets/mm3, and increased within 24 h after stopping rhGM-CSF treatment, whereas marrow histology after 2 weeks of rhGM-CSF application showed the normal number and morphology of megakaryocytes.
评估了重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)对犬造血功能的影响。rhGM-CSF可刺激去除辅助细胞的犬骨髓的粒细胞巨噬细胞集落形成,刺激倍数高达10倍。抗rhGM-CSF抗血清或热灭活可消除集落形成刺激。rhGM-CSF以持续静脉输注和间歇性皮下注射给药时,均能刺激犬的体内造血功能。中性粒细胞、单核细胞和淋巴细胞计数比对照组增加了三到八倍,而嗜酸性粒细胞、网织红细胞和血细胞比容的值没有变化。用rhGM-CSF治疗2周后的骨髓组织学显示细胞增多,伴有髓系增生和粒细胞生成左移。停用rhGM-CSF后,外周白细胞计数在3-7天内恢复到对照水平。开始使用rhGM-CSF后血小板计数迅速下降至5000-15,000个血小板/mm3,并在停止rhGM-CSF治疗后24小时内升高,而应用rhGM-CSF 2周后的骨髓组织学显示巨核细胞数量和形态正常。