Granulocyte macrophage colony-stimulating factor
|Colony stimulating factor 2 (granulocyte-macrophage)|
PDB rendering based on 2gmf
|RNA expression pattern|
|Granulocyte-macrophage colony-stimulating factor|
three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor
|Systematic (IUPAC) name|
|Human granulocyte macrophage colony stimulating factor|
|(what is this?)|
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
GM-CSF is a monomeric glycoprotein that functions as a cytokine - it is a white blood cell growth factor. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and 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 infection. GM-CSF signals via signal transducer and activator of transcription, STAT5.
GM-CSF signals via signal transducer and activator of transcription, STAT5. In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of 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.
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 5q- syndrome and acute myelogenous leukemia. Genes in the cluster include those encoding interleukins 4, 5, and 13.
Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.
GM-CSF is manufactured using recombinant DNA technology and is marketed as a protein therapeutic called molgramostim or, when the protein is expressed in yeast cells, sargramostim. It is used as a medication to stimulate the production of white blood cells and thus prevent neutropenia following chemotherapy.
GM-CSF has also recently been evaluated in clinical trials for its potential as a vaccine adjuvant in HIV-infected patients. The preliminary results have been promising but GM-CSF is not presently FDA-approved for this purpose.
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 Goiânia accident. It was originally developed by Immunex. When Amgen bought Immunex, sargramostim was divested to Berlex, a US subsidiary of Schering AG. Berlex was acquired by Bayer in 2006, and Bayer sold the franchise to Genzyme in 2009, which was subsequently acquired by Sanofi. Its use was approved by U.S. Food and Drug Administration for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma, acute lymphocytic leukemia, or 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.
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