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 Ortholog search: PDBe, RCSB List of PDB id codes 1CSG, 2GMF, 3CXE
Identifiers
Symbols	CSF2 ; GMCSF
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 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 • macrophage activation • positive regulation of tyrosine phosphorylation of Stat5 protein • myeloid dendritic cell differentiation • positive regulation of DNA replication • negative regulation of cytolysis • cellular response to lipopolysaccharide • positive regulation of podosome assembly • dendritic cell differentiation • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Sources: Amigo / QuickGO
RNA expression pattern
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: 132.07 – 132.08 Mb	Chr 11: 54.25 – 54.25 Mb
PubMed search	[1]	[2]

Granulocyte-macrophage colony-stimulating factor
File: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
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Granulocyte macrophage colony-stimulating factor

Systematic (IUPAC) name
Human granulocyte macrophage colony stimulating factor
Identifiers
CAS Number	83869-56-1 Y
ATC code	L03AA09 (WHO)
DrugBank	DB00020 N
Chemical data
Formula	C639H1006N168O196S8
Molecular mass	14434.5 g/mol
NY (what is this?)  (verify)

Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.

Function

GM-CSF is a monomeric glycoprotein that functions as a cytokine - it is 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.

GM-CSF also has some effects on mature cells of the immune system. These include, for example, inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface.

GM-CSF signals via signal transducer and activator of transcription, STAT5. In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity. Thus, GM-CSF facilitates development of the immune system and promotes defense against infections.

GM-CSF also plays a role in embryonic development by functioning as an embryokine produced by reproductive tract.

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.

Glycosylation

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

Medical use

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.

GM-CSF has also been evaluated in clinical trials for its potential as a vaccine adjuvant in HIV-infected patients.

Sargramostim

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 cesium irradiation from the Goiânia accident. It was originally developed by Immunex. When Amgen bought Immunex, sargramostim was divested to Berlex, a US subsidiary of Schering AG. Berlex was acquired by Bayer in 2006, and Bayer sold the franchise to Genzyme in 2009, which was subsequently acquired by Sanofi. 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 fungal infections and replenishment of white blood cells following chemotherapy.

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 (e.g. MOR103) are being developed to block GM-CSF.

See also

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

External links

• Official gentaur web site
• Official Leukine web site
• Granulocyte-Macrophage Colony-Stimulating Factor at the US National Library of Medicine Medical Subject Headings (MeSH)