G-CSF preferentially supports the generation of gut-homing Gr-1high macrophages in M-CSF-treated bone marrow cells

J Leukoc Biol. 2014 Oct;96(4):549-61. doi: 10.1189/jlb.1A0314-172R. Epub 2014 Jun 30.

Abstract

The G-CSF is best known for its activity in the generation and activation of neutrophils. In addition, studies on G-CSF(-/-) or G-CSFR(-/-) mice and BMC cultures suggested a role of G-CSF in macrophage generation. However, our understanding on the role of G-CSF in macrophage development is limited. Here, using in vitro BMC models, we demonstrated that G-CSF promoted the generation of Gr-1(high)/F4/80(+) macrophage-like cells in M-BMCs, likely through suppressing cell death and enhancing generation of Gr-1(high)/F4/80(+) macrophage-like cells. These Gr-1(high) macrophage-like cells produced "M2-like" cytokines and surface markers in response to LPS and IL-4/IL-13, respectively. Adoptive transfer of EGFP-expressing (EGFP(+)) M-BMCs showed a dominant, gut-homing phenotype. The small intestinal lamina propria of G-CSFR(-/-) mice also harbored significantly reduced numbers of Gr-1(high)/F4/80(+) macrophages compared with those of WT mice, but levels of Gr-1(+)/F4/80(-) neutrophil-like cells were similar between these mice. Collectively, these results suggest a novel function of G-CSF in the generation of gut-homing, M2-like macrophages.

Keywords: GM-CSF; differentiation; myeloid cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • Antigens, Surface / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Female
  • Gastrointestinal Tract / cytology*
  • Gastrointestinal Tract / immunology*
  • Granulocyte Colony-Stimulating Factor / genetics
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Immunophenotyping
  • Macrophage Colony-Stimulating Factor / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*

Substances

  • Antigens, Ly
  • Antigens, Surface
  • Cytokines
  • Ly-6C antigen, mouse
  • Receptors, Cell Surface
  • granulocyte receptor 1, mouse
  • Granulocyte Colony-Stimulating Factor
  • Macrophage Colony-Stimulating Factor