Medlock E S, Kaplan D L, Cecchini M, Ulich T R, del Castillo J, Andresen J
Department of Experimental Hematology, Amgen Inc, Thousand Oaks, CA 91320.
Blood. 1993 Feb 15;81(4):916-22.
We studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.
我们研究了给怀孕大鼠注射重组人粒细胞集落刺激因子（rhG-CSF）对胎儿及新生儿骨髓生成的影响。在分娩前2天、4天和6天，每天给怀孕大鼠注射rhG-CSF两次。rhG-CSF可穿过胎盘，并在给药后4小时达到胎儿血清浓度峰值。胎儿血清峰值水平比母鼠体内检测到的水平低1000倍。通过对新生儿的血液、脾脏、骨髓、胸腺和肝脏进行细胞学分析，评估rhG-CSF的造血作用。新生儿白细胞计数增加了两倍至四倍。这种增加是由于多形核细胞（PMN）的循环数量增加所致。rhG-CSF在出生后第2天和第4天接受治疗的幼崽中，诱导新生儿骨髓出现髓样增生，包括未成熟和成熟的髓样细胞。接受6天治疗的幼崽骨髓中大多是核分叶过多的PMN，髓样前体细胞几乎没有增加或没有增加。在新生儿脾脏中观察到有丝分裂后（PMN、带状核细胞和晚幼粒细胞）和有丝分裂期（早幼粒细胞、原粒细胞和中幼粒细胞）髓样细胞数量增加。脾脏淋巴细胞或单核细胞未检测到变化。在新生儿肝脏或胸腺中未发现rhG-CSF有作用。这些结果表明，母体给予的rhG-CSF可穿过胎盘，并特异性地诱导胎儿和新生儿的骨髓及脾脏骨髓生成。rhG-CSF在胎儿体内低浓度时具有显著的骨髓生成作用，表明对这种细胞因子具有高度的发育敏感性，并可能为新生儿提供增强的防御机制。
