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

• Published in: The Journal of immunology (1950) Vol. 202; no. 9; pp. 2700 - 2709
• Main Authors: Draijer, Christina, Penke, Loka Raghu Kumar, Peters-Golden, Marc
• Format: Journal Article
• Language: English
• Published: United States 01.05.2019
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1801387

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.