Macrophage colony-stimulating factor

The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted is_associated_with::cytokine which influences is_associated_with::hematopoietic stem cells to differentiate into is_associated_with::macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. (See is_associated_with::colony-stimulating factor.) M-CSF binds to the is_associated_with::Colony stimulating factor 1 receptor. It may also be involved in development of the is_associated_with::placenta.

Structure
M-CSF is a is_associated_with::cytokine. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors.

Four transcript variants encoding three different isoforms have been found for this gene.

Function
M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the proliferation, differentiation, and survival of is_associated_with::monocytes, is_associated_with::macrophages, and bone marrow progenitor cells. M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumour cell cytotoxicity. The role of M-CSF is not only restricted to the monocyte/macrophage cell lineage. By interacting with its membrane receptor (is_associated_with::CSF1R or M-CSF-R encoded by the c-fms proto-oncogene), M-CSF also modulates the proliferation of earlier hematopoietic progenitors and influence numerous physiological processes involved in immunology, metabolism, fertility and pregnancy.

M-CSF released by is_associated_with::osteoblasts (as a result of is_associated_with::endocrine stimulation by is_associated_with::parathyroid hormone) exerts is_associated_with::paracrine effects on is_associated_with::osteoclasts. M-CSF binds to receptors on is_associated_with::osteoclasts inducing differentiation, and ultimately leading to increased plasma is_associated_with::calcium levels—through the is_associated_with::resorption (breakdown) of bone. Additionally, high levels of CSF-1 expression are observed in the endometrial epithelium of the pregnant uterus as well as high levels of its receptor is_associated_with::CSF1R in the placental is_associated_with::trophoblast. Studies have shown that activation of trophoblasitc CSF1R by local high levels of CSF-1 is essential for normal embryonic implantation and placental development. More recently, it was discovered that CSF-1 and its receptor is_associated_with::CSF1R are implicated in the mammary gland during normal development and is_associated_with::neoplastic growth.

Clinical significance
Locally produced M-CSF in the vessel wall contributes to the development and progression of is_associated_with::atherosclerosis.

In addition, M-CSF has been described to play a role in the chronic activation of monocytes leading to multiple metabolic, hematologic and immunologic abnormalities in patients with Chronic Renal Failure (CRF).

Interactions
Macrophage colony-stimulating factor has been shown to interact with is_associated_with::PIK3R2.