View source for Granulocyte macrophage colony stimulating factor

{{distinguish|granulocyte colony-stimulating factor}}

{{drugbox
| IUPAC_name = Human granulocyte macrophage colony stimulating factor
| image = GMCSF_Crystal_Structure.rsh.png
| CAS_number = 83869-56-1
| ATC_prefix = L03
| ATC_suffix = AA09 
| ATC_supplemental = 
| PubChem = 
| DrugBank = BTD00035
| C=639 | H=1006 | N=168 | O=196 | S=8
| molecular_weight = 14434.5 g/mol
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| pregnancy_category = 
| legal_status = 
| routes_of_administration = 
}}
{{PBB_Controls
| update_page = yes 
| require_manual_inspection = no 
| update_protein_box = yes
| update_summary = no
| update_citations = yes
}}
{{GNF_Protein_box
 | image = GMCSF_Crystal_Structure.rsh.png
 | image_source = [[Protein_Data_Bank|PDB]] rendering based on 2gmf
 | Name = Colony stimulating factor 2 (granulocyte-macrophage)
 | HGNCid = 2434
 | Symbol = CSF2
 | AltSymbols =; GMCSF; MGC131935; MGC138897
 | OMIM = 138960
 | ECnumber =  
 | Homologene = 600
 | MGIid = 1339752
 | GeneAtlas_image1 = PBB_GE_CSF2_210229_s_at_tn.png
 | Function = {{GNF_GO|id=GO:0005125 |text = cytokine activity}} {{GNF_GO|id=GO:0005129 |text = granulocyte macrophage colony-stimulating factor receptor binding}} 
 | Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} 
 | Process = {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0006968 |text = cellular defense response}} {{GNF_GO|id=GO:0007166 |text = cell surface receptor linked signal transduction}} {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0043011 |text = myeloid dendritic cell differentiation}} {{GNF_GO|id=GO:0045885 |text = positive regulation of survival gene product activity}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1437
    | Hs_Ensembl = ENSG00000164400
    | Hs_RefseqProtein = NP_000749
    | Hs_RefseqmRNA = NM_000758
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 131437382
    | Hs_GenLoc_end = 131439758
    | Hs_Uniprot = P04141
    | Mm_EntrezGene = 12981
    | Mm_Ensembl = ENSMUSG00000018916
    | Mm_RefseqmRNA = NM_009969
    | Mm_RefseqProtein = NP_034099
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 54090687
    | Mm_GenLoc_end = 54093065
    | Mm_Uniprot = Q14AD9
  }}
}}
{{SI}}
{{CMG}}
==Overview==
'''Granulocyte-macrophage colony-stimulating factor''', often abbreviated to '''GM-CSF''', is a [[protein]] secreted by [[macrophage]]s, [[T cell]]s, [[mast cells]], [[endothelial cell]]s and [[fibroblast]]s. 

==Functions==
GM-CSF is a [[cytokine]] that functions as a [[white blood cell]] [[growth factor]]. GM-CSF stimulates [[stem cell]]s to produce [[granulocyte]]s ([[neutrophil]]s, [[eosinophil]]s, and [[basophil]]s) and [[monocyte]]s. Monocytes exit the circulation and migrate into tissue, whereupon they mature into [[macrophage]]s. It is thus part of the [[immune system|immune]]/[[inflammation|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]]. Other genes in the cluster include those encoding [[Interleukin 4|interleukins 4]], [[Interleukin 5|5]], and [[Interleukin 13|13]].<ref>{{cite web | title = Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1437| accessdate = }}</ref>

==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]]) (see US Patent No. 5,073,627).<ref>http://www.google.com/patents?vid=USPAT5073627&dq=5,073,627</ref>

==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 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.<ref> [http://www.accessdata.fda.gov/scripts/cder/onctools/yearlistclaim.cfm?Approv_Date=1991] Details of Approved Claims by Line of Therapy, Approved Claims for 1991, FDA.gov</ref> In November 1996, the FDA also approved sargramostim for treatment of [[fungal infection]]s and replenishment of  white blood cells following chemotherapy.<ref> [http://www.centerwatch.com/patient/drugs/dru179.html] Drugs Approved by the FDA, Drug Name: Leukine (sargramostim), CenterWatch.com</ref>

===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]].<ref>{{cite journal |author=Korzenik J, Dieckgraefe B, Valentine J, Hausman D, Gilbert M |title=Sargramostim for active Crohn's disease |journal=N Engl J Med |volume=352 |issue=21 |pages=2193-201 |year=2005 |id=PMID 15917384}}</ref>

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.<ref name="phoenix">[http://www.thephoenix.com/Article.aspx?id=8920&page=1 "Med school drug pushers: How scientists are selling out to drug companies"], by David S. Bernstein, The Phoenix. Published April 12 2006. Accessed 8 Feb 2007.</ref> 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.<ref name="phoenix"/>

==See also==
* [[Granulocyte macrophage colony-stimulating factor receptor]]

==References==
{{reflist|2}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Esnault S, Malter JS |title=GM-CSF regulation in eosinophils. |journal=Arch. Immunol. Ther. Exp. (Warsz.) |volume=50 |issue= 2 |pages= 121-30 |year= 2002 |pmid= 12022701 |doi=  }}
*{{cite journal  | author=Martinez-Moczygemba M, Huston DP |title=Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF. |journal=J. Allergy Clin. Immunol. |volume=112 |issue= 4 |pages= 653-65; quiz 666 |year= 2003 |pmid= 14564341 |doi= 10.1016/S0091 }}
*{{cite journal  | author=Mroczko B, Szmitkowski M |title=Hematopoietic cytokines as tumor markers. |journal=Clin. Chem. Lab. Med. |volume=42 |issue= 12 |pages= 1347-54 |year= 2005 |pmid= 15576295 |doi= 10.1515/CCLM.2004.253 }}
*{{cite journal  | author=Hamilton JA, Anderson GP |title=GM-CSF Biology. |journal=Growth Factors |volume=22 |issue= 4 |pages= 225-31 |year= 2005 |pmid= 15621725 |doi= 10.1080/08977190412331279881 }}
*{{cite journal  | author=Tortorella C, Simone O, Piazzolla G, ''et al.'' |title=Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. |journal=Ageing Res. Rev. |volume=6 |issue= 2 |pages= 81-93 |year= 2007 |pmid= 17142110 |doi= 10.1016/j.arr.2006.10.001 }}
*{{cite journal  | author=Robertson SA |title=GM-CSF regulation of embryo development and pregnancy. |journal=Cytokine Growth Factor Rev. |volume=18 |issue= 3-4 |pages= 287-98 |year= 2007 |pmid= 17512774 |doi= 10.1016/j.cytogfr.2007.04.008 }}
}}
{{refend}}

==External links==
* [http://www.leukine.com/ http://www.leukine.com/ - Official Leukine web site]
* {{MeshName|Granulocyte-Macrophage+Colony-Stimulating+Factor}}

[[Category:Immunology]]
[[Category:Hematology]]
[[Category:Growth factors]]

{{Colony-stimulating factors}}

[[es:Factor estimulante de colonias de granulocito y macrófagos]]
[[ja:GM-CSF]]
[[pl:Czynnik stymulujący tworzenie kolonii granulocytów i makrofagów]]
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