Mobilization with granulocyte colony-stimulating factor blocks medullar erythropoiesis by depleting F4/80(+)VCAM1(+)CD169(+)ER-HR3(+)Ly6G(+) erythroid island macrophages in the mouse.
Similarly to other tissues, the bone marrow contains subsets of resident tissue macrophages, which are essential to maintain bone formation, functional hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering with the HSC niche-supportive function of BM resident macrophages. Because bone marrow macrophages are key to both maintenance of HSC within their niche and erythropoiesis, we investigated the effect of mobilizing doses of G-CSF on erythropoiesis in mice. We now report that G-CSF blocks medullar erythropoiesis by depleting the erythroid island macrophages we identified as co-expressing F4/80, vascular cell adhesion molecule-1, CD169, Ly-6G, and the ER-HR3 erythroid island macrophage antigen. Both broad macrophage depletion, achieved by injecting clodronate-loaded liposomes, and selective depletion of CD169(+) macrophages, also concomitantly depleted F4/80(+)VCAM-1(+)CD169(+)ER-HR3(+)Ly-6G(+) erythroid island macrophages and blocked erythropoiesis. This more precise phenotypic definition of erythroid island macrophages will enable studies on their biology and function in normal settings and on diseases associated with anemia. Finally, this study further illustrates that macrophages are a potent relay of innate immunity and inflammation on bone, hematopoietic, and erythropoietic maintenance. Agents that affect these macrophages, such as G-CSF, are likely to affect these three processes concomitantly.
Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia; School of Medicine, University of Queensland, Saint Lucia, Queensland, Australia.
Rebecca N
RN
Jacobsen
Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Catherine E
CE
Forristal
Bones and Immunology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Liza J
LJ
Raggatt
Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Bianca
B
Nowlan
Stem Cells and Cancer Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Valerie
V
Barbier
Bones and Immunology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Simranpreet
S
Kaur
Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands.
Nico
N
van Rooijen
Stem Cells and Cancer Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Ingrid G
IG
Winkler
Bones and Immunology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia.
Allison R
AR
Pettit
Stem Cell Biology Group, Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia; School of Medicine, University of Queensland, Saint Lucia, Queensland, Australia. Electronic address: jplevesque@mmri.mater.org.au.
Jean-Pierre
JP
Levesque
D000818:Animals; D004920:Erythropoiesis / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D019010:Vascular Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor