Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF.
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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D006098:Granulocytes / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007958:Leukocyte Count; D008251:Macaca; D008253:Macaca mulatta; D008264:Macrophages / Q000032:analysis; D010198:Pancytopenia / Q000188:drug therapy; D011994:Recombinant Proteins / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins