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.
Functions [ edit ]
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.
Genetics [ edit ]
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. [1 ]
Glycosylation [ edit ]
Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.
Medical use [ edit ]
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 ( Leukine). 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. [2 ]
Leukine [ edit ]
Leukine is the trade name of 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 [3 ] 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 [4 ] fungal infections and replenishment of white blood cells following chemotherapy. [5 ]
Rheumatoid arthritis [ edit ]
GM-CSF is found in high levels in joints with
rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs (e.g. MOR103) are being developed to block GM-CSF. [6 ]
See also [ edit ]
References [ edit ]
External links [ edit ]
1csg: THREE-DIMENSIONAL STRUCTURE OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR
2gmf: HUMAN GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR