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|
|Mol. mass||14434.5 g/mol|
|(what is this?)|
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony stimulating factor 2 (CSF2), is a protein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
GM-CSF is a cytokine that functions as 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. The active form of the protein is found extracellularly as a homodimer. 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 (see Zinc sequestration by GM-CSF). 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 the Goiânia cesium irradiation accident. It is currently manufactured by Berlex Laboratories, a subsidiary of Schering AG. 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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- Official gentaur web site
- Official Leukine web site
- Granulocyte-Macrophage Colony-Stimulating Factor at the US National Library of Medicine Medical Subject Headings (MeSH)