Granulocyte macrophage colony-stimulating factor

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Not to be confused with granulocyte colony-stimulating factor.
Colony stimulating factor 2 (granulocyte-macrophage)
GMCSF Crystal Structure.rsh.png
PDB rendering based on 2gmf
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CSF2 ; GMCSF
External IDs OMIM138960 MGI1339752 HomoloGene600 GeneCards: CSF2 Gene
RNA expression pattern
PBB GE CSF2 210229 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1437 12981
Ensembl ENSG00000164400 ENSMUSG00000018916
UniProt P04141 P01587
RefSeq (mRNA) NM_000758 NM_009969
RefSeq (protein) NP_000749 NP_034099
Location (UCSC) Chr 5:
131.41 – 131.41 Mb
Chr 11:
54.25 – 54.25 Mb
PubMed search [1] [2]
Granulocyte-macrophage colony-stimulating factor
PDB 1csg EBI.jpg
three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor
Identifiers
Symbol GM_CSF
Pfam PF01109
Pfam clan CL0053
InterPro IPR000773
PROSITE PDOC00584
SCOP 2gmf
SUPERFAMILY 2gmf
Granulocyte macrophage colony-stimulating factor
GMCSF Crystal Structure.rsh.png
Systematic (IUPAC) name
Human granulocyte macrophage colony stimulating factor
Clinical data
Legal status
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Identifiers
CAS number 83869-56-1 YesY
ATC code L03AA09
DrugBank DB00020
Chemical data
Formula C639H1006N168O196S8 
Mol. mass 14434.5 g/mol
 N (what is this?)  (verify)

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.[1] 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.[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[5] but GM-CSF is not presently FDA-approved for this purpose.

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.[6] 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.[7] In November 1996, the FDA also approved sargramostim for treatment of 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]

  1. ^ 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. 
  2. ^ Voehringer D (2012). "Basophil modulation by cytokine instruction". Eur. J. Immunol. 42 (10): 2544–50. doi:10.1002/eji.201142318. PMID 23042651. 
  3. ^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)". 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ Schmeck HM (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug". New York Times. Retrieved 2012-06-20. 
  7. ^ "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. 
  8. ^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. Retrieved 2008-10-12. 
  9. ^ 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]