Granulocyte macrophage colony stimulating factor exerts dominant effects over macrophage colony stimulating factor during macrophage differentiation in vitro to induce an inflammatory phenotype.

Abstract

Macrophages (Mφ) can exist along a spectrum of phenotypes that include pro-inflammatory (M1) or anti-inflammatory (M2) immune cells. Mφ colony stimulating factor (M-CSF) and granulocyte Mφ colony stimulating factor (GM-CSF) are cytokines important in hematopoiesis, polarization and activation of Mφ. To gain a greater understanding of the relationship between GM-CSF and M-CSF, we investigated an in vitro model of differentiation to determine if GM-CSF and M-CSF can antagonize each other, in terms of Mφ phenotype and functions. We determined that Mφ cultured in mixed M-CSF: GM-CSF ratios exhibit M1-like GM-CSF-treated macrophage phenotype when the ratios of the two cytokines are 1:1 in culture. Moreover, GM-CSF is dominant over M-CSF in influencing Mφ production of proinflammatory cytokines such as IL-6, TNFα, and IL-12p40, and the anti-inflammatory cytokine IL-10. Our data established that GM-CSF is more dominant over M-CSF, triggering the Mφ to become pro-inflammatory cells. These findings provide insight into how GM-CSF can influence Mφ activation with implications in inflammatory diseases where the Mφ status can play a significant role in supporting the inflammatory conditions.