Murine megakaryocyte progenitor cells and their susceptibility to suppression by G-CSF.
In agar cultures of mouse bone marrow cells, mega-karyocyte colony-forming cells exhibited shorter survival times than granulocyte-macrophage progenitor cells when initially cultured in the absence of stimulating factors. Initiation of cultures with G-CSF improved the survival times of granulocyte-macrophage progenitor cells and those of megakaryocyte progenitor cells. Paradoxically, G-CSF was found to consistently inhibit megakaryocyte colony formation stimulated by erythropoietin or by stem cell factor plus interleukin-3 (IL-3) plus erythropoietin. G-CSF was a less-consistent inhibitor of megakaryocyte colonies stimulated by thrombopoietin or IL-3. Analysis of the response of marrow cells from mice with the deletion of the genes encoding CIS, SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS-6, or SOCS-7 indicated that the inhibitory SOCS proteins, with the possible exception of SOCS-3, were not involved in the G-CSF-initiated suppression of megakaryocyte colony formation.
Metcalf
Donald
D
Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. metcalf@wehi.edu.au
Mifsud
Sandra
S
Di Rago
Ladina
L
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay / Q000379:methods; D004921:Erythropoietin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D016014:Linear Models; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019089:Stem Cell Factor / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D013926:Thrombopoietin / Q000494:pharmacology; D013997:Time Factors
D007377:Interleukin-3; D019089:Stem Cell Factor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin