Granulocyte macrophage colony-stimulating factor

Not to be confused with granulocyte colony-stimulating factor.

Colony stimulating factor 2 (granulocyte-macrophage)
PDB rendering based on 2gmf
Available structures PDB 1CSG, 2GMF, 3CXE
Identifiers
Symbols	CSF2; GMCSF; MGC131935; MGC138897
External IDs	OMIM: 138960 MGI: 1339752 HomoloGene: 600 GeneCards: CSF2 Gene
Gene Ontology Molecular function • cytokine activity • granulocyte macrophage colony-stimulating factor receptor binding • protein binding • growth factor activity Cellular component • extracellular region • extracellular region • extracellular space Biological process • embryonic placenta development • immune response • positive regulation of cell proliferation • positive regulation of gene expression • positive regulation of macrophage derived foam cell differentiation • positive regulation of interleukin-23 production • epithelial fluid transport • positive regulation of tyrosine phosphorylation of Stat5 protein • myeloid dendritic cell differentiation • negative regulation of apoptosis • positive regulation of DNA replication • positive regulation of survival gene product expression • negative regulation of cytolysis • positive regulation of podosome assembly Sources: Amigo / QuickGO
RNA expression pattern
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
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
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

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.

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

• Granulocyte macrophage colony-stimulating factor receptor
• CFU-GM

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

• Esnault S, Malter JS (2002). "GM-CSF regulation in eosinophils". Arch. Immunol. Ther. Exp. (Warsz.) 50 (2): 121–30. PMID 12022701. 
• Martinez-Moczygemba M, Huston DP (2003). "Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF". J. Allergy Clin. Immunol. 112 (4): 653–65; quiz 666. doi:10.1016/j.jaci.2003.08.015. PMID 14564341. 
• Mroczko B, Szmitkowski M (2005). "Hematopoietic cytokines as tumor markers". Clin. Chem. Lab. Med. 42 (12): 1347–54. doi:10.1515/CCLM.2004.253. PMID 15576295. 
• Hamilton JA, Anderson GP (2005). "GM-CSF Biology". Growth Factors 22 (4): 225–31. doi:10.1080/08977190412331279881. PMID 15621725. 
• Tortorella C, Simone O, Piazzolla G et al. (2007). "Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins". Ageing Res. Rev. 6 (2): 81–93. doi:10.1016/j.arr.2006.10.001. PMID 17142110. 
• Robertson SA (2007). "GM-CSF regulation of embryo development and pregnancy". Cytokine Growth Factor Rev. 18 (3–4): 287–98. doi:10.1016/j.cytogfr.2007.04.008. PMID 17512774. 
• Morales JK, Kmieciak M, Knutson KL, Bear HD, Manjili MH (2009). "GM-CSF is one of the main breast tumor-derived soluble factors involved in the differentiation of CD11b−Gr1− bone marrow progenitor cells into myeloid-derived suppressor cells". Breast Cancer Res Treat. 123 (1): 39–49. doi:10.1007/s10549-009-0622-8. PMC 3095485. PMID 19898981. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3095485. 

External links

• http://www.gm-csf.com/ - Official gentaur web site
• http://www.leukine.com/ - Official Leukine web site
• MeSH Granulocyte-Macrophage+Colony-Stimulating+Factor