Scheding S, Media J E, Kraut M, Valdivieso M, Nakeff A
Division of Hematology and Oncology, Wayne State University, School of Medicine, Detroit, Michigan 48201.
Br J Haematol. 1994 Dec;88(4):699-705. doi: 10.1111/j.1365-2141.1994.tb05107.x.
The aim of this study was to systematically characterize possible rhG-CSF effects on the murine megakaryocyte-platelet system (untreated and recovering from chemotherapy or extramedullary irradiation). In untreated, splenectomized male B6D2F1 mice, rhG-CSF treatment (50 micrograms/kg/d for up to 8 d) markedly decreased femoral megakaryocytopoiesis. CFU-Meg, small acetylcholinesterase-positive (SAChE) cells, and megakaryocytes were significantly reduced to 35-70%; platelets, however, were not affected. Peripheral CFU-Meg and CFU-GM increased up to 200-fold. Following a single injection of 5-FU (150 mg/kg) on day 0, rhG-CSF (50 micrograms/kg/d) on days 1-8 suppressed the megakaryocytopoietic recovery as indicated by significantly lower platelet numbers on day 9. Granulopoietic recovery was accelerated by rhG-CSF. When rhG-CSF treatment was started on day 5, no beneficial effect on granulopoietic recovery was observed, but again platelet levels were significantly lower on day 9, indicating that within the first 4 d of rhG-CSF application, recruitment or lineage competition was not a critical event. To test for the effects of extramedullary irradiation on circulating progenitors, mice pretreated with 50 micrograms/kg/d of rhG-CSF for 8 d received irradiation to the chest with 500 cGy resulting in a substantial kill of circulating CFU-Meg and CFU-GM of up to 99%. However, this striking decrease of blood progenitors did not significantly affect their total body contents. This study indicates that rhG-CSF treatment can impair bone marrow megakaryocytopoiesis, which might be an important consideration for those clinical situations that carry a high potential for treatment-induced thrombocytopenia.
本研究的目的是系统地描述重组人粒细胞集落刺激因子（rhG-CSF）对小鼠巨核细胞-血小板系统（未处理以及化疗或髓外照射后恢复阶段）可能产生的影响。在未处理的、脾切除的雄性B6D2F1小鼠中，rhG-CSF治疗（50微克/千克/天，持续8天）显著降低了股骨巨核细胞生成。巨核细胞集落形成单位（CFU-Meg）、小乙酰胆碱酯酶阳性（SAChE）细胞和巨核细胞显著减少至35%-70%；然而，血小板未受影响。外周血CFU-Meg和CFU-GM增加至200倍。在第0天单次注射5-氟尿嘧啶（5-FU，150毫克/千克）后，第1-8天给予rhG-CSF（50微克/千克/天）抑制了巨核细胞生成的恢复，表现为第9天血小板数量显著降低。rhG-CSF加速了粒细胞生成的恢复。当在第5天开始rhG-CSF治疗时，未观察到对粒细胞生成恢复有有益作用，但第9天血小板水平再次显著降低，表明在rhG-CSF应用的前4天内，募集或谱系竞争不是关键事件。为了测试髓外照射对循环祖细胞的影响，用50微克/千克/天的rhG-CSF预处理8天的小鼠接受500 cGy的胸部照射，导致循环CFU-Meg和CFU-GM大量死亡，高达99%。然而，血液祖细胞的这种显著减少并未显著影响其全身含量。本研究表明，rhG-CSF治疗可能损害骨髓巨核细胞生成，这对于那些具有治疗诱导血小板减少高风险的临床情况可能是一个重要的考虑因素。
