Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF
Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF
复制标题
连续输注重组人 GM-CSF 刺激灵长类动物造血
作者：
R. Donahue;E. A. Wang;David K. Stone;R. Kamen;G. Wong;P. Sehgal;D. Nathan;S. Clark
已知某些蛋白质在体外造血祖细胞的增殖、分化和功能活化中发挥重要作用1，2。这些蛋白质包括促红细胞生成素和各种集落刺激因子（CSF），其中之一是粒细胞-巨噬细胞集落刺激因子（GM-CSF）。最近，鼠3、4和人GM-CSF 5 -7都已被纯化至同质，并且编码它们的互补DNA已被克隆。尽管重组人GM-CSF的体外活性已被深入研究（参考文献5-15;综述见参考文献8），但对该蛋白在体内的功能活性知之甚少。有强有力的证据表明，由各种人类和小鼠肿瘤组织和细胞系产生的集落刺激活性可以刺激小鼠的粒细胞生成16 -26，人尿提取物也可以27，28。然而，部分纯化的人尿集落刺激因子制剂在刺激人类粒细胞生成方面仅证明是轻微有效的29。所有这些研究都缺乏均匀的集落刺激因子制剂。最近已经表明，重组鼠多CSF或白细胞介素-3可以刺激小鼠体内造血30，31。大规模生产的重组人GM-CSF现在允许我们检查其在体内使用灵长类动物模型的影响。我们发现，在健康猴中持续输注GM-CSF可迅速诱发显著的白细胞增多和大量的网织红细胞增多。在一只全血细胞减少、免疫缺陷的恒河猴中观察到了类似的效果。这些结果表明，GM-CSF可以证明在几种临床情况下是有用的。
Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro1,2. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte–macrophage colony-stimulating factor (GM-CSF). Recently, both murine3,4 and human GM-CSF5–7 have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively (refs 5–15; see ref. 8 for a review), little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice16–26, as can human urinary extracts27,28. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans29. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo30,31. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations.
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影响培养物中造血细胞生长和分化的因素。
DOI：
--
发表时间：
1984
期刊：
Clinics in haematology
影响因子：
--
作者：
Stanley,ER;Jubinsky,PT
通讯作者：
Jubinsky,PT
纯化人骨髓祖细胞增殖的诱导：粒细胞集落刺激因子的快速测定。
影响因子：
20.3
作者：
Griffin,JD;Sullivan,R;Beveridge,RP;Larcom,P;Schlossman,SF
通讯作者：
Schlossman,SF
DOI：
10.1002/stem.5530030203
发表时间：
1985
期刊：
International journal of cell cloning
影响因子：
--
作者：
G. Johnson;N. Nicola;R. Whitehead
通讯作者：
G. Johnson;N. Nicola;R. Whitehead
重组人粒细胞-巨噬细胞集落刺激因子的体外生物学特性。
影响因子：
20.3
作者：
Metcalf,D;Begley,CG;Johnson,GR;Nicola,NA;Vadas,MA;Lopez,AF;Williamson,DJ;Wong,GG;Clark,SC;Wang,EA
通讯作者：
Wang,EA
影响因子：
56.9
作者：
GASSON, JC;WEISBART, RH;GOLDE, DW
通讯作者：
GOLDE, DW