Polarized macrophage functions are affected differentially after CSF-1R inhibition with PLX5622

Eur J Pharmacol. 2024 Dec 5:984:177059. doi: 10.1016/j.ejphar.2024.177059. Epub 2024 Oct 16.

Abstract

PLX5622 is a colony stimulating factor 1 receptor (CSF-1R) inhibitor that is known to deplete microglial cells in vivo. Recently its effects on macrophages (Mφ) were also observed in vivo. Therefore, we performed this study to assess its in vitro effects on the differentiation and functions of polarized Mφ derived from different tissues. Our findings show that addition of PLX5622 early on after ex vivo isolation hinders Mφ differentiation and survival. However, its addition post Mφ differentiation did not significantly affect the viability. Furthermore, PLX5622 affects certain functions and degree of polarization of IL-4 (M2a) Mφ but not polarization of M1-like Mφ. Our study provides novel aspects on the application of PLX5622 to study Mφ functions in vitro, where polarization is affected by CSF-1R signalling and provides distinctive evidence to its ability to affect certain populations of Mφ during in vitro differentiation and maturation.

Keywords: CSF-1R; Cytokines; M-CSF; Polarization.

MeSH terms

  • Animals
  • Cell Differentiation* / drug effects
  • Cell Polarity / drug effects
  • Cell Survival / drug effects
  • Humans
  • Interleukin-4 / metabolism
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Mice
  • Organic Chemicals
  • Receptor, Macrophage Colony-Stimulating Factor* / antagonists & inhibitors
  • Receptor, Macrophage Colony-Stimulating Factor* / metabolism

Substances

  • Receptor, Macrophage Colony-Stimulating Factor
  • PLX5622
  • Interleukin-4
  • Organic Chemicals