Colony-stimulating factors (CSFs) are secreted glycoproteins. They bind to receptor proteins on the surfaces of hemopoietic stem cells. By doing this, CSFs activate intracellular signaling pathways that can cause the cells to proliferate and differentiate into a specific kind of blood cell (usually white blood cells. For red blood cell formation, see erythropoietin). Compared to other membrane-bound substances of the hematopoietic microenvironment, colony-stimulating factors are soluble. They transduce by paracrine, endocrine, or autocrine signaling. Colony-stimulating factors include CSF1, CSF2 and CSF3.
Colony-stimulating factor 1, also known as MCSF and CSF1, is a secreted cytokine which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. MCSF controls the survival, proliferation, and differentiation of mononuclear phagocytes and regulates cells of the females reproductive tract. MCSF may also play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, and myeloid and lymphoid tissues. Through alternative mRNA splicing and differential post-translational proteolytic processing, CSF-1 can either be secreted into the circulation as a glycoprotein or chondroitin sulfate-containing proteoglycan or be expressed as a membrane-spanning glycoprotein on the surface of CSF-1-producing cells.
Granulocyte-macrophage colony-stimulating factor, also known as GM-CSF and CSF2, is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. GM-CSF gene has been localized to a cluster of related genes at chromosome region 5q31. The active form of the protein is found extracellularly as a homodimer. GM-CSF can be used as a medication to stimulate the production of white blood cells following chemotherapy. It may also be used as a vaccine adjuvant in HIV-infected patients. GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage.
Colony stimulating factor 3 (granulocyte), also known as G-CSF and CSF3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. G-CSF stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils. G-CSF is a potent inducer of HSCs mobilization from the bone marrow into the bloodstream, although it has been shown that it does not directly affect the hematopoietic progenitors that are mobilized. Beside the effect on the hematopoietic system, G-CSF can also act on neuronal cells as a neurotrophic factor. Indeed, its receptor is expressed by neurons in the brain and spinal cord. The action of G-CSF in the central nervous system is to induce neurogenesis, to increase the neuroplasticity and to counteract apoptosis. These properties are currently under investigations for the development of treatments of neurological diseases such as cerebral ischemia.