Macrophage colony stimulating factor

The macrophage colony-stimulating factor, M-CSF (Macrophage colony-stimulating factor), is an endogenous protein from the group of cytokines. M-CSF is encoded by the M-CSF gene, which is located on chromosome 1: 109.91 - 109.93. The active form of M-CSF is found extracellularly. It is formed by proteolytic cleavage from a membrane-bound precursor molecule.

M-CSF is a ligand for the colony stimulating factor 1 receptor M-CSF-R (also called CSF1R) which is expressed on numerous cells. M-CSF controls the proliferation of hematopoietic progenitor cells and influences numerous immune processes. In detail, M-CSF regulates the density of tissue macrophages and monocyte populations without changing their activation status (Ushach I et al. 2016). M-CSF thus proves to be a functional opponent of GM-CSF.

M-CSF also plays an important role in fertility and pregnancy. It has been shown that the activation of CSF1R in trophoblasts by high CSF-1 levels is essential for the implantation of the embryo and for the further development of the placenta (Jones CV et al. 2013).

Under the influence of M-CSF, monocytes differentiate into M-CSF macrophages, whose activation by IFN gamma and LPS leads to inflammatory M1 macrophages with cytotoxic properties. The activation of M-CSF macrophages with the interleukins IL-4 and IL-10 leads to M2-macrophages.

Osteoblasts secrete (parathormone induced) M-CSF. This binds to precursor cells of osteoclasts and stimulates their maturation and proliferation.

M-CSF is produced by numerous tumor cell lines. Tumour-associated macrophages, also known as TAMs (see below as macrophages), are attracted by an increased expression of M-CSFR-1 receptors. This promotes tumour progression and metastasis (Laoui D et al. 2014; Sullivan AR et al. 2014). From such experimental observations, which are now reliable, therapeutic options can be derived for oncological questions (Laoui D et al. 2014).

1. Chockalingam S et al(2014) Macrophage colony-stimulating factor and cancer: a review. Tumour Biol 35:10635 10644.
2. Hume DA et al (2012)Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood 119:1810-1820.
3. Jones CV et al (2013) Macrophages and CSF-1: implications for development and beyond. Organogenesis 9:249-260.
4. Laoui D et al (2014) Functional Relationship between Tumor-Associated Macrophages and Macrophage Colony-Stimulating Factor as Contributors to Cancer Progression. Front Immunol 5:489.
5. Sullivan AR et al (2014) CSF-1R signaling in health and disease: a focus on the mammary gland. J Mammary Gland Biol Neoplasia 19:149-159.
6. Ushach I et al (2016) Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol 100:481-489.