Distinctive Effects of GM-CSF and M-CSF on Proliferation and Polarization of Two Major Pulmonary Macrophage Populations

J Immunol. 2019 May 1;202(9):2700-2709. doi: 10.4049/jimmunol.1801387. Epub 2019 Mar 13.

Abstract

GM-CSF is required for alveolar macrophage (AM) development shortly after birth and for maintenance of AM functions throughout life, whereas M-CSF is broadly important for macrophage differentiation and self-renewal. However, the comparative actions of GM-CSF and M-CSF on AMs are incompletely understood. Interstitial macrophages (IMs) constitute a second major pulmonary macrophage population. However, unlike AMs, IM responses to CSFs are largely unknown. Proliferation, phenotypic identity, and M1/M2 polarization are important attributes of all macrophage populations, and in this study, we compared their modulation by GM-CSF and M-CSF in murine primary AMs and IMs. CSFs increased the proliferation capacity and upregulated antiapoptotic gene expression in AMs but not IMs. GM-CSF, but not M-CSF, reinforced the cellular identity, as identified by surface markers, of both cell types. GM-CSF, but not M-CSF, increased the expression of both M1 and M2 markers exclusively in AMs. Finally, CSFs enhanced the IFN-γ- and IL-4-induced polarization ability of AMs but not IMs. These first (to our knowledge) data comparing effects on the two pulmonary macrophage populations demonstrate that the activating actions of GM-CSF and M-CSF on primary AMs are not conserved in primary IMs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / immunology
  • Cell Proliferation / drug effects*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Interferon-gamma / immunology*
  • Interleukin-4 / immunology*
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophage Colony-Stimulating Factor / pharmacology*
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / immunology*
  • Male
  • Mice

Substances

  • Antigens, Differentiation
  • IFNG protein, mouse
  • Il4 protein, mouse
  • Interleukin-4
  • Macrophage Colony-Stimulating Factor
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor