The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor.
The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor.
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DOI：
10.1182/blood.v78.4.961.bloodjournal784961
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发表时间：
1991-08
期刊：
影响因子：
20.3
通讯作者：
G. Molineux;A. Migdalska;M. Szmitkowski;K. Zsebo;T. Dexter
中科院分区：
文献类型：
--
作者：
G. Molineux;A. Migdalska;M. Szmitkowski;K. Zsebo;T. Dexter
干细胞因子（SCF）是c-kit原癌基因编码的受体的配体。c-kit或SCF基因的突变导致W和SI突变小鼠的缺陷，这两种小鼠都患有大红细胞性贫血，前者与有缺陷的干细胞相关，后者与有缺陷的造血微环境相关。将PEG化重组大鼠SCF给予正常或脾切除小鼠长达21天。SCF被发现是一个温和的刺激外周血中性粒细胞数量在两组动物。中性粒细胞数量的峰值更高，并且在脾切除小鼠中更早出现。治疗期间骨髓和脾细胞结构变化不大，但白细胞介素-3反应性祖细胞和脾集落形成细胞（CFU-S）的含量达到非常高的水平，特别是在脾脏中。使用重组人粒细胞集落刺激因子（rhG-CSF），我们已经表明，SCF诱导血液中性粒细胞和血源性CFU-S的增加大于相加。这种协同作用在整个剂量范围内都可以看到，这可能表明SCF单独或在增强G-CSF对血液中性粒细胞和可移植干细胞的活性方面具有临床作用。
Stem cell factor (SCF) is the ligand for the receptor encoded by the c-kit proto-oncogene. Mutations of either c-kit or the SCF gene are responsible for the defects of W and SI mutant mice, which both suffer a macrocytic anemia, the former associated with defective stem cells and the latter with a defective hematopoietic microenvironment. PEGylated recombinant rat SCF was administered to normal or splenectomized mice for up to 21 days. SCF was found to be a modest stimulator of peripheral blood neutrophil numbers in both groups of animals. The peak in neutrophil numbers was higher and occurred earlier in splenectomized mice. Bone marrow and spleen cellularity changed little during treatment but the content of interleukin-3-responsive progenitor cells and spleen colony-forming cells (CFU-S) reached very high levels, particularly in the spleen. Using recombinant human granulocyte colony-stimulating factor (rhG-CSF), we have shown that SCF induces a greater than additive increase in both blood neutrophils and blood-borne CFU-S. This synergy was seen throughout the dose range and may indicate a clinical role for SCF either alone or in augmenting the activity of G-CSF upon blood neutrophils and transplantable stem cells.