title: Synergistic effect of stem cell factor with interleukin-3 or granulocyte-macrophage colony-stimulating factor on the proliferation of murine primitive hematopoietic progenitors.
abstract: We examined the effect of recombinant murine stem cell factor (SCF) on murine primitive hematopoietic stem cells in vivo. Marrow cells from 5-fluorouracil (5-FU)-treated male CBA/J mice were transplanted into lethally irradiated female littermates. Immediately after marrow transplant, the mice received SCF, interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination daily for 6 days. Day-12 colony-forming units-spleen (CFU-S) and marrow-derived colony-forming units-granulocyte/macrophage (CFU-GM) were assessed. Bone marrow cells from primary transplant recipients were transplanted into a secondary group of lethally irradiated mice, and the number of spleen colonies arising after 12 days' engraftment was determined as pre-CFU-S. SCF alone did not increase spleen colony formation in either primary or secondary recipients. In contrast, treatment of primary recipients with SCF and GM-CSF or IL-3 or with all three cytokines resulted in a synergistic increase of CFU-S in secondary recipients, indicating increased pre-CFU-S levels. The cytokine combinations also produced synergistic increases of CFU-GM in primary recipient marrow. Evaluation of spleen colonies in secondary recipients by PCR amplification of the Y-chromosome sex-determining region indicated that about 80% were of donor (male) origin. We conclude that SCF with IL-3 and/or GM-CSF increases pre-CFU-S proliferation.
authors.affiliation: Canadian Red Cross Society, Toronto Centre.
authors.forename: D D
authors.initials: DD
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Nayar
authors.forename: A
authors.initials: A
authors.lastname: Keating
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000473:pathology*; D004357:Drug Synergism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007377:Interleukin-3 / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D019089:Stem Cell Factor
chemical_list: D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor