Molecular physiology of granulocyte-macrophage colony-stimulating factor

Abstract

H cess in the adult, where about 3 x lo9 erythroid cells/kg and lo9 myeloid celis/kg are generated each day. Twenty-five years ago, in vitro assays were developed to detect factors that could stimulate the growth of colonies from immature bone marrow (BM)-derived progenitors.'.' These systems have made it possible to identify and characterize the factors regulating myelopoiesis. The application of molecular biologic approaches to study hematopoiesis facilitated the cloning of genes encoding the hematopoietic growth factors and their production in mammalian cells, yeast, and bacteria in quantities sufficient for in vitro and in vivo studies. Granulocyte-macrophage colonystimulating factor (GM-CSF) is one of a family of glycoprotein cytokines that have potent effects in stimulating proliferation, maturation, and function of hematopoietic cells. Although GM-CSF was the first, several hematopoietic growth factors are now used in clinical trials. Most of the effects observed using GM-CSF in vitro have been shown to occur in vivo either in animal models or in human subjects. In this review, I shall summarize the basic science studies on GM-CSF, because others have recently reviewed the literature on the clinical applications of GM-CSF and other hematopoietins.'-' GENOMIC ORGANIZATION AND CHROMOSOMAL LOCALIZATION

Granulocyte–macropha ge colony‐stimulating factor down‐regulates CD14 expression on monocytes

“…This was remarkable because GM-CSF induces differentiation of myeloid lineage cells and enhances CD14 expression on promonocytic cell lines cultured with vitamin D 3 , 15,16 and because it activates mature macrophages and granulocytes. 17 Moreover, GM-CSF enhanced CD14 expression on neutrophils. The mechanism responsible for this down-regulation of CD14 on monocytes has been explored and its potential significance is discussed.…”

c‐Rel and p65 subunits bind to an upstream NF‐κB site in human granulocyte macrophage‐colony stimulating factor promoter involved in phorbol ester response in 5637 cells

“…GM-CSF is a glycoprotein cytokine involved in hematopoiesis and host defense [1]. With regard to the transcriptional control of GM-CSF gene expression, a distal and a proximal promoter region have been investigated.…”

Granulocyte macrophage-colony stimulating factor stimulates both association and activation of phosphoinositide 3OH-kinase and src-related tyrosine kinase(s) in human myeloid derived cells.

“…The cytokine GM-CSF (granulocyte macrophage-colony stimulating factor) has a variety of actions on myeloid derived cells; it has been shown to stimulate mitogenesis, differentiation, increased cell viability, increased synthesis/release of other extracellular mediators and priming/activation of mature cell function (reviewed in Gasson, 1991;Rapoport, 1992). The basic lack of understanding of how many of these responses are controlled and, more subtly, the fact that some of them involve effects on the signalling pathways of other ligands (e.g.…”