Donahue R E, Wang E A, Stone D K, Kamen R, Wong G G, Sehgal P K, Nathan D G, Clark S C
Nature. 1986;321(6073):872-5. doi: 10.1038/321872a0.
Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte-macrophage colony-stimulating factor (GM-CSF). Recently, both murine and human GM-CSF 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, 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 mice, as can human urinary extracts. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans. 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 vivo. 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.
已知某些蛋白质在体外造血祖细胞的增殖、分化和功能激活中起重要作用。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，小鼠和人类的GM-CSF均已纯化至同质，并且编码它们的互补DNA已被克隆。尽管对重组人GM-CSF的体外活性进行了深入研究，但对该蛋白在体内的功能活性了解甚少。有强有力的证据表明，各种人类和小鼠肿瘤组织及细胞系产生的集落刺激活性可刺激小鼠的粒细胞生成，人类尿液提取物也能如此。然而，一种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显示出微弱的效果。所有这些研究都因缺乏集落刺激因子的同质制剂而受到影响。最近有研究表明，重组小鼠多集落刺激因子或白细胞介素-3可在体内刺激小鼠造血。重组人GM-CSF的大规模生产现在使我们能够使用灵长类动物模型来研究其在体内的作用。我们发现，在健康猴子中持续输注GM-CSF会迅速引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也观察到了类似的效果。这些结果表明，GM-CSF在几种临床情况下可能会证明是有用的。
