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.
Function [ edit ]
GM-CSF is a
cytokine that functions as a white blood cell growth factor. GM-CSF stimulates [1 ] 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. [2 ]
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. [3 ]
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. It is used as a medication to stimulate the production of white blood cells and thus prevent neutropenia following chemotherapy. [4 ]
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. [5 ]
Sargramostim [ edit ]
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 [6 ] 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 [7 ] fungal infections and replenishment of white blood cells following chemotherapy. [8 ]
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. [9 ]
See also [ edit ]
References [ edit ]
^ Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R (2014). "Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor". Med. Oncol. 31 (1): 774. doi: 10.1007/s12032-013-0774-6. PMID 24264600.
^ Voehringer D (2012). "Basophil modulation by cytokine instruction". Eur. J. Immunol. 42 (10): 2544–50. doi: 10.1002/eji.201142318. PMID 23042651.
^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)".
^ Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L (2013). "Trial Watch: Immunostimulatory cytokines". Oncoimmunology 2 (7): e24850. doi: 10.4161/onci.24850. PMC 3782010. PMID 24073369.
^ Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R, Pelusio A, Le Boeuf F, Burns J, Evgin L, De Silva N, Cvancic S, Robertson T, Je JE, Lee YS, Parato K, Diallo JS, Fenster A, Daneshmand M, Bell JC, Kirn DH (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature 477 (7362): 99–102. doi: 10.1038/nature10358. PMID 21886163.
^ Schmeck HM (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug". New York Times . Retrieved 2012-06-20.
^ "Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 1991-03-05. Archived from the original on 2007-09-29 . Retrieved 20 September 2009.
^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch . Retrieved 2008-10-12.
^ Deiß A, Brecht I, Haarmann A, Buttmann M (2013). "Treating multiple sclerosis with monoclonal antibodies: a 2013 update". Expert Rev Neurother 13 (3): 313–35. doi: 10.1586/ern.13.17. PMID 23448220.
External links [ edit ]
1csg: THREE-DIMENSIONAL STRUCTURE OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR
2gmf: HUMAN GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR