Identification of a common signal associated with cellular proliferation stimulated by four haemopoietic growth factors in a highly enriched population of granulocyte/macrophage colony-forming cells.
We have prepared a population of bone marrow cells that is highly enriched in neutrophil/macrophage progenitor cells (GM-CFC). Four distinct haemopoietic growth factors can stimulate the formation of mature cells from this population, although the proportions of neutrophils and/or macrophages produced varied depending on the growth factor employed: interleukin 3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) stimulated the formation of colonies containing both neutrophils and macrophages; macrophage colony-stimulating factor (M-CSF) produced predominantly macrophage colonies; and granulocyte colony-stimulating factor (G-CSF) promoted neutrophil colony formation. Combinations of these four growth factors did not lead to any additive or synergistic effect on the number of colonies produced in clonal soft agar assays, indicating the presence of a common set of cells responsive to all four haemopoietic growth factors. These enriched progenitor cells therefore represent an ideal population to study myeloid growth-factor-stimulated survival, proliferation and development. Using this population we have examined the molecular signalling mechanisms associated with progenitor cell proliferation. We have shown that modulation of cyclic AMP levels has no apparent role in GM-CFC proliferation, whereas phorbol esters and/or Ca2+ ionophore can stimulate DNA synthesis, indicating a possible role for protein kinase C activation and increased cytosolic Ca2+ levels in the proliferation of these cells. The lack of ability of all four myeloid growth factors to mobilize intracellular Ca2+ infers that these effects are not achieved via inositol lipid hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cook
N
N
Department of Biochemistry and Applied Molecular Biology, UMIST, UK.
Dexter
T M
TM
Lord
B I
BI
Cragoe
E J
EJ
Whetton
A D
AD
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D015222:Sodium Channels / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D015222:Sodium Channels; D000584:Amiloride; D004247:DNA; C056369:5-(N-methyl-N-isobutyl)amiloride; D002118:Calcium; D013936:Thymidine