title: Fms-like tyrosine kinase 3 (Flt3) ligand depletes erythroid island macrophages and blocks medullar erythropoiesis in the mouse.
abstract: The cytokines granulocyte colony-stimulating factor (G-CSF) and Flt3 ligand (Flt3-L) mobilize hematopoietic stem and progenitor cells into the peripheral blood of primates, humans, and mice. We recently reported that G-CSF administration causes a transient blockade of medullar erythropoiesis by suppressing erythroblastic island (EI) macrophages in the bone marrow. In the study described here, we investigated the effect of mobilizing doses of Flt3-L on erythropoiesis in mice in vivo. Similar to G-CSF, Flt3-L caused whitening of the bone marrow with significant reduction in the numbers of EI macrophages and erythroblasts. This was compensated by an increase in the numbers of EI macrophages and erythroblasts in the spleen. However, unlike G-CSF, Flt3-L had an indirect effect on EI macrophages, as it was not detected at the surface of EI macrophages or erythroid progenitors.
authors.affiliation: Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia; School of Medicine, University of Queensland, Herston, Queensland, Australia.
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Jacobsen
authors.affiliation: Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
authors.forename: Bianca
authors.initials: B
authors.lastname: Nowlan
authors.affiliation: Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
authors.forename: Marion E
authors.initials: ME
authors.lastname: Brunck
authors.affiliation: Stem Cells and Cancer Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
authors.forename: Valerie
authors.initials: V
authors.lastname: Barbier
authors.affiliation: Stem Cells and Cancer Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
authors.forename: Ingrid G
authors.initials: IG
authors.lastname: Winkler
authors.affiliation: Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia; School of Medicine, University of Queensland, Herston, Queensland, Australia. Electronic address: jp.levesque@mater.uq.edu.au.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Levesque
mesh_terms: D000818:Animals; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3