Granulocyte macrophage colony-stimulating factor

Colony stimulating factor 2 (granulocyte-macrophage)

PDB rendering based on 2gmf
Identifiers
Symbols CSF2; GMCSF; MGC131935; MGC138897
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 Q14AD9
RefSeq (mRNA) NM_000758.2 NM_009969.4
RefSeq (protein) NP_000749.2 NP_034099.2
Location (UCSC) Chr 5:
131.41 – 131.41 Mb
Chr 11:
54.06 – 54.06 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
Granulocyte macrophage colony-stimulating factor
Systematic (IUPAC) name
Human granulocyte macrophage colony stimulating factor
Clinical data
Pregnancy cat.  ?
Legal status  ?
Identifiers
CAS number 83869-56-1
ATC code L03AA09
DrugBank BTD00035
Chemical data
Formula C639H1006N168O196S8 
Mol. mass 14434.5 g/mol

Granulocyte-macrophage colony-stimulating factor, often abbreviated to GM-CSF, is a protein secreted by macrophages, T cells, mast cells, endothelial cells, and fibroblasts.

Contents

Functions

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

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

Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.

Clinical significance

GM-CSF is also known as molgramostim or, when the protein is expressed in yeast cells, sargramostim (Leukine).

GM-CSF is used as a medication to stimulate the production of white blood cells 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[2] but GM-CSF is not presently FDA-approved for this purpose.

Leukine

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.[3] 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.[3] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.[4]

Controversy

Berlex funded a study that ran in the May 26, 2005 issue of the New England Journal of Medicine, which concluded that GM-CSF did produce significantly more remissions in Crohn's disease than those having received a placebo in the study, and it also decreased disease severity and improved quality of life.[5]

The study's lead author, Joshua Korzenik of Harvard Medical School and Massachusetts General Hospital, is a paid consultant for Berlex , and co-inventor of the patent, which is owned by Washington University.[6]

Rheumatoid arthritis

GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs (eg MOR103) are being developed to block GM-CSF.[7]

See also

References

  1. ^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1437. 
  2. ^ Breitbach CJ, et al. (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature 477 (7362): 99–102. doi:10.1038/nature10358. PMID 21886163. 
  3. ^ "Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 5 March 1991. Archived from the original on 29 September 2007. http://web.archive.org/web/20070624223312/www.accessdata.fda.gov/scripts/cder/onctools/summary.cfm?ID=353. Retrieved 20 September 2009. 
  4. ^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. http://www.centerwatch.com/patient/drugs/dru179.html. Retrieved 12 October 2008. 
  5. ^ Korzenik J, Dieckgraefe B, Valentine J, Hausman D, Gilbert M (2005). "Sargramostim for active Crohn's disease". N Engl J Med 352 (21): 2193–201. doi:10.1056/NEJMoa041109. PMID 15917384. 
  6. ^ Bernstein DS (2006-04-12). "Med school drug pushers: How scientists are selling out to drug companies". The Boston Phoenix. http://www.thephoenix.com/Article.aspx?id=8920&page=1. Retrieved 2008-10-12. 
  7. ^ "MOR103 - Antibody for the Treatment of Rheumatoid Arthritis, Germany". 2010. http://www.drugdevelopment-technology.com/projects/mor103/. 

Further reading

External links


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