title: Regulation of granulocyte and macrophage populations of murine bone marrow cells by G-CSF and CD137 protein.
abstract: BACKGROUND
  Granulocytes and monocytes/macrophages differentiate from common myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, respectively. This study describes the influence of G-CSF and recombinant CD137-Fc protein on myelopoiesis.
  
  
  RESULTS
  Both, G-CSF and CD137 protein support proliferation and survival of murine bone marrow cells. G-CSF enhances granulocyte numbers while CD137 protein enhances macrophage numbers. Both growth factors together give rise to more cells than each factor alone. Titration of G-CSF and CD137 protein dose-dependently changes the granulocyte/macrophage ratio in bone marrow cells. Both factors individually induce proliferation of hematopoietic progenitor cells (lin-, c-kit+) and differentiation to granulocytes and macrophages, respectively. The combination of G-CSF and CD137 protein further increases proliferation, and results in a higher number of macrophages than CD137 protein alone, and a lower number of granulocytes than G-CSF alone demonstrating that CD137 protein-induced monocytic differentiation is dominant over G-CSF-induced granulocytic differentiation. CD137 protein induces monocytic differentiation even in early hematopoietic progenitor cells, the common myeloid progenitors and the granulocyte macrophage progenitors.
  
  
  CONCLUSIONS
  This study confirms earlier data on the regulation of myelopoiesis by CD137 receptor - ligand interaction, and extends them by demonstrating the restriction of this growth promoting influence to the monocytic lineage.
authors.affiliation: Department of Physiology, and Immunology Programme, Yong Loo Lin School of Medicine, Singapore, Singapore.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Jiang
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D004950:Esterases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D011994:Recombinant Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D016179:Granulocyte Colony-Stimulating Factor; D004950:Esterases