granulocyte-macrophage colony-stimulating factor

Colony stimulating factor 2 (granulocyte-macrophage)
PDB rendering based on 2gmf
Available structures
1csg, 2gmf
Identifiers
Symbols	CSF2; GMCSF; MGC131935; MGC138897
External IDs	OMIM: 138960 MGI: 1339752 HomoloGene: 600
Gene ontology Molecular function • cytokine activity • granulocyte macrophage colony-stimulating factor receptor binding Cellular component • extracellular region • extracellular space Biological process • immune response • cellular defense response • cell surface receptor linked signal transduction • multicellular organismal development • positive regulation of cell proliferation • myeloid dendritic cell differentiation • positive regulation of survival gene product activity
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1437	12981
Ensembl	ENSG00000164400	ENSMUSG00000018916
UniProt	P04141	Q14AD9
RefSeq	NM_000758 (mRNA)	NM_009969 (mRNA)
	NP_000749 (protein)	NP_034099 (protein)
Location	Chr 5: 131.44 - 131.44 Mb	Chr 11: 54.09 - 54.09 Mb
PubMed search	[1]	[2]

Granulocyte macrophage colony-stimulating factor
Systematic (IUPAC) name
Human granulocyte macrophage colony stimulating factor
Identifiers
CAS number	83869-56-1
ATC code	L03AA09
PubChem	?
DrugBank	BTD00035
Chemical data
Formula	C639H1006N168O196S8
Mol. mass	14434.5 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

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. It is thus 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 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. The glycosylation sites are reported to be at amino acid residues 23 (leucine), 27 (asparagine), and 39 (glutamic acid).^[2]

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. It 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.

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 who 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] Korzenik created a "firewall" to protect the integrity of the study, consisting of two committees to review the study results and process as well and sending trial data to outside clinicians for review.^[6]

See also

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

References

Further reading

v • d • e PDB Gallery 1csg: THREE-DIMENSIONAL STRUCTURE OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR   2gmf: HUMAN GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR

External links

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