Granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the density of stem cell factor receptors (c-kit oncogene product) on a GM-CSF-dependent human myeloid cell line

Eur Cytokine Netw. 1993 Jul-Aug;4(4):293-7.

Abstract

By employing a monoclonal antibody against the stem cell factor receptor (SCF-R), c-kit oncogene product, we analysed in flow cytometric technique the density of SCF-R on GM/SO cells which were incubated under various culture conditions. These experiments revealed that there is an inverse correlation between the SCF-R density on the cells and the doses of granulocyte-macrophage colony-stimulating factor (GM-CSF) in culture medium; the lower the dose, the higher the density of SCF-R on the cells. More detailed analyses showed that, in contrast to SCF which rapidly downregulates its own receptor, GM-CSF does not alter the measurable level of SCF-R in an exposition period of 60 minutes, which suggests that the internalization or shedding of the receptor is not the mechanism of action. Since the most striking difference regarding density of SCF-R between GM-CSF-treated and untreated cells was observed on day 2, the modulation of c-kit oncogene protein by GM-CSF likely occur prior to expression of protein onto the cell surface. In order to exclude the possibility that altered cell viability due to insufficient GM-CSF content in culture medium might be responsible for the increased SCF-R densities on GM-CSF-dependent cells, we subsequently generated a GM-CSF-independent subclone which still responded to GM-CSF as well as the dependent did. The experiments carried out with this subclone confirmed the results presented above. Thus our data suggest that GM-CSF is directly involved in the regulation of SCF receptor density on GM/SO cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Line, Transformed
  • Down-Regulation / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Cell Growth Factors / metabolism*
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptors, Colony-Stimulating Factor / biosynthesis*
  • Receptors, Colony-Stimulating Factor / immunology
  • Recombinant Proteins / pharmacology
  • Stem Cell Factor

Substances

  • Antibodies, Monoclonal
  • Hematopoietic Cell Growth Factors
  • Proto-Oncogene Proteins
  • Receptors, Colony-Stimulating Factor
  • Recombinant Proteins
  • Stem Cell Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases