Colony stimulating factors and macrophage heterogeneity

Abstract

Macrophages or mononuclear phagocytes are heterogeneous populations present throughout the body which can adapt quite dramatically to the surrounding milieu, both in the steady state and during immune/inflammatory responses. To assist in our understanding of this diversity, they have been classified into polarization or " activation " states, termed M1 and M2, respec-tively. This in vitro classification commonly incorporates interferon γ (± lipopolysaccharide) as the stimulus for M1 macrophages and IL-4 or IL-13 for M2 macrophages. Attempts are un-derway to place tissue macrophages, isolated from ongoing immune/inflammatory reactions, into these categories. However, more flexible classifications are needed to take into account the diversity of macrophage functions. We have compared the in vitro properties of mono-cytes/macrophages treated with macrophage-colony stimulating factor (M-CSF or CSF-1) and granulocyte macrophage-CSF (GM-CSF), the former because of its role in macrophage lineage development in the steady state and the latter because of its proinflammatory and im-mune-potentiating properties. Data will be presented on " M2-like " properties of CSF-1-treated populations and " M1-like " features of the GM-CSF-treated counterparts with links to IL-12 family biology. It is proposed that such CSF-dependent changes should be considered in dis-cussions of macrophage polarization. The concept of " CSF-1 resistance " in macrophages, whereby steady state CSF-1-dependent signaling has to be overcome by pro-inflammatory stimuli, such as GM-CSF, interferon γ etc, will be discussed.