Granulocyte macrophage colony-stimulating factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony stimulating factor 2 (CSF2), is a is_associated_with::monomeric is_associated_with::glycoprotein secreted by is_associated_with::macrophages, is_associated_with::T cells, is_associated_with::mast cells, is_associated_with::NK cells, is_associated_with::endothelial cells and is_associated_with::fibroblasts that functions as a is_associated_with::cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called is_associated_with::sargramostim and is_associated_with::molgramostim.

Function
GM-CSF is a is_associated_with::monomeric is_associated_with::glycoprotein that functions as a is_associated_with::cytokine - it is a is_associated_with::white blood cell is_associated_with::growth factor. GM-CSF stimulates is_associated_with::stem cells to produce is_associated_with::granulocytes (is_associated_with::neutrophils, is_associated_with::eosinophils, and is_associated_with::basophils) and is_associated_with::monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into is_associated_with::macrophages and is_associated_with::dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting is_associated_with::infection. GM-CSF signals via signal transducer and activator of transcription, is_associated_with::STAT5.

GM-CSF signals via signal transducer and activator of transcription, is_associated_with::STAT5. In macrophages, it has also been shown to signal via is_associated_with::STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of is_associated_with::reactive oxygen species that culminate in fungal zinc starvation and toxicity. Thus, GM-CSF facilitates development of the immune system and promotes defense against infections.

GM-CSF also plays a role in embryonic development by functioning as an is_associated_with::embryokine produced by reproductive tract.

Genetics
The human gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the is_associated_with::5q- syndrome and is_associated_with::acute myelogenous leukemia. Genes in the cluster include those encoding interleukins 4, 5, and 13.

Glycosylation
Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.

Medical use
GM-CSF is manufactured using is_associated_with::recombinant DNA technology and is marketed as a protein therapeutic called is_associated_with::molgramostim or, when the protein is expressed in is_associated_with::yeast cells, is_associated_with::sargramostim. It is used as a medication to stimulate the production of white blood cells and thus prevent is_associated_with::neutropenia following is_associated_with::chemotherapy.

GM-CSF has also recently been evaluated in clinical trials for its potential as a vaccine is_associated_with::adjuvant in HIV-infected patients. The preliminary results have been promising but GM-CSF is not presently FDA-approved for this purpose.

Sargramostim
is_associated_with::Sargramostim, recombinant yeast-derived GM-CSF developed at Immunex (now Amgen) and first given to six humans in 1987 as part of a compassionate-use protocol for the victims of cesium irradiation from the is_associated_with::Goiânia accident. It was originally developed by is_associated_with::Immunex. When is_associated_with::Amgen bought Immunex, sargramostim was divested to is_associated_with::Berlex, a US subsidiary of is_associated_with::Schering AG. Berlex was acquired by is_associated_with::Bayer in 2006, and Bayer sold the franchise to is_associated_with::Genzyme in 2009, which was subsequently acquired by is_associated_with::Sanofi. Its use was approved by U.S. is_associated_with::Food and Drug Administration for acceleration of white blood cell recovery following autologous is_associated_with::bone marrow transplantation in patients with is_associated_with::non-Hodgkin's lymphoma, is_associated_with::acute lymphocytic leukemia, or is_associated_with::Hodgkin's disease in March 1991. In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.

Rheumatoid arthritis
GM-CSF is found in high levels in joints with is_associated_with::rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs (e.g. is_associated_with::MOR103) are being developed to block GM-CSF.