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'''Granulocyte-macrophage colony-stimulating factor''' ('''GM-CSF'''), also known as '''colony stimulating factor 2 (CSF2)''', is a [[protein]] secreted by [[macrophage]]s, [[T cell]]s, [[mast cells]], [[NK cells]], [[endothelial cell]]s and [[fibroblast]]s. The [[pharmaceutical drug|pharmaceutical]] analogs of naturally occurring GM-CSF are called [[sargramostim]] and [[molgramostim]].
'''Granulocyte-macrophage colony-stimulating factor''' ('''GM-CSF'''), also known as '''colony stimulating factor 2 (CSF2)''', is a [[protein]] secreted by [[macrophage]]s, [[T cell]]s, [[mast cells]], [[NK cells]], [[endothelial cell]]s and [[fibroblast]]s. The [[pharmaceutical drug|pharmaceutical]] analogs of naturally occurring GM-CSF are called [[sargramostim]] and [[molgramostim]].


==Functions==
== Functions ==
GM-CSF is a [[cytokine]] that functions as a [[white blood cell]] [[growth factor]].<Ref>Francisco-Cruz A et al. Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor. Med Oncol. 2014 Jan;31(1):774. doi: 10.1007/s12032-013-0774-6. Epub 2013 Nov 22. PMID 24264600</ref> 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 and [[dendritic cell]]s. Thus, it is part of the [[immune system|immune]]/[[inflammation|inflammatory]] [[biochemical cascade|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]]. GM-CSF signals via signal transducer and activator of transcription, [[STAT5]].<ref>Voehringer D. Basophil modulation by cytokine instruction. Eur J Immunol. 2012 Oct;42(10):2544-50. doi: 10.1002/eji.201142318. PMID 23042651</ref>
GM-CSF is a [[cytokine]] that functions as a [[white blood cell]] [[growth factor]].<ref name="pmid24264600">{{cite journal | author = Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R | title = Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor | journal = Med. Oncol. | volume = 31 | issue = 1 | pages = 774 | year = 2014 | pmid = 24264600 | doi = 10.1007/s12032-013-0774-6 | url = }}</ref> 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 and [[dendritic cell]]s. Thus, it is part of the [[immune system|immune]]/[[inflammation|inflammatory]] [[biochemical cascade|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]]. GM-CSF signals via signal transducer and activator of transcription, [[STAT5]].<ref name="pmid23042651">{{cite journal | author = Voehringer D | title = Basophil modulation by cytokine instruction | journal = Eur. J. Immunol. | volume = 42 | issue = 10 | pages = 2544–50 | year = 2012 | pmid = 23042651 | doi = 10.1002/eji.201142318 }}</ref>


==Genetics==
== Genetic s==
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 [[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>
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 [[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==
== Glycosylation ==
Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.
Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.


==Medical use==
== Medical use ==


GM-CSF is manufactured using [[recombinant DNA]] technology and is marketed as a [[Biologic medical product|protein therapeutic]] called [[molgramostim]] or, when the protein is expressed in [[yeast]] cells, [[sargramostim]] ('''Leukine'''). It is used as a medication to stimulate the production of white blood cells and thus prevent [[neutropenia]] following [[chemotherapy]].<ref>Vacchelli E et al. Trial Watch: Immunostimulatory cytokines. Oncoimmunology. 2013 Jul 1;2(7):e24850. Epub 2013 May 7. PMID 24073369</ref>
GM-CSF is manufactured using [[recombinant DNA]] technology and is marketed as a [[Biologic medical product|protein therapeutic]] called [[molgramostim]] or, when the protein is expressed in [[yeast]] cells, [[sargramostim]] ('''Leukine'''). It is used as a medication to stimulate the production of white blood cells and thus prevent [[neutropenia]] following [[chemotherapy]].<ref name="pmid24073369">{{cite journal | author = Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L | title = Trial Watch: Immunostimulatory cytokines | journal = Oncoimmunology | volume = 2 | issue = 7 | pages = e24850 | year = 2013 | pmid = 24073369 | pmc = 3782010 | doi = 10.4161/onci.24850 }}</ref>


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<ref name=Natureref>{{Cite journal | author=Breitbach CJ, et al. |title=Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans |journal=Nature |volume=477 |issue= 7362 |pages= 99–102 |year= 2011 |pmid= 21886163 |doi= 10.1038/nature10358 }}</ref> but GM-CSF is not presently FDA-approved for this purpose.
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<ref name=Natureref>{{cite journal | author = Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R, Pelusio A, Le Boeuf F, Burns J, Evgin L, De Silva N, Cvancic S, Robertson T, Je JE, Lee YS, Parato K, Diallo JS, Fenster A, Daneshmand M, Bell JC, Kirn DH | title = Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans | journal = Nature | volume = 477 | issue = 7362 | pages = 99–102 | year = 2011 | pmid = 21886163 | doi = 10.1038/nature10358 }}</ref> but GM-CSF is not presently FDA-approved for this purpose.


===Leukine===
===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.<ref>{{cite web|author=By HAROLD M. SCHMECK JrPublished: November 02, 1987 |url=http://www.nytimes.com/1987/11/02/world/radiation-team-sent-to-brazil-saves-two-with-a-new-drug.html |title=Radiation Team Sent to Brazil Saves Two With a New Drug - New York Times |publisher=Nytimes.com |date=1987-11-02 |accessdate=2012-06-20}}</ref> 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.<ref name="urlDetails of Approved Claims by Line of Therapy">{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/onctools/yearlistclaim.cfm?Approv_Date=1991 |title=Approval Summary for sargramostim |accessdate=20 September 2009 |date=5 March 1991 |work=Oncology Tools |publisher=U.S. Food and Drug Administration, Center for Drug Evaluation and Research |archiveurl=http://web.archive.org/web/20070624223312/www.accessdata.fda.gov/scripts/cder/onctools/summary.cfm?ID=353 |archivedate=29 September 2007 }}</ref> In November 1996, the FDA also approved sargramostim for treatment of [[Fungal infection in animals|fungal infection]]s and replenishment of white blood cells following chemotherapy.<ref name="urlNewly Approved Drug Therapies (179): Leukine (sargramostim), Immunex">{{cite web| url = http://www.centerwatch.com/patient/drugs/dru179.html | title = Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex | author = | authorlink = | coauthors = | date = | work = | publisher = CenterWatch | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 12 October 2008}}</ref>
''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.<ref>{{cite web|author=By HAROLD M. SCHMECK JrPublished: November 02, 1987 |url=http://www.nytimes.com/1987/11/02/world/radiation-team-sent-to-brazil-saves-two-with-a-new-drug.html |title=Radiation Team Sent to Brazil Saves Two With a New Drug - New York Times |publisher=Nytimes.com |date=1987-11-02 |accessdate=2012-06-20}}</ref> 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.<ref name="urlDetails of Approved Claims by Line of Therapy">{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/onctools/yearlistclaim.cfm?Approv_Date=1991 |title=Approval Summary for sargramostim |accessdate=20 September 2009 |date=5 March 1991 |work=Oncology Tools |publisher=U.S. Food and Drug Administration, Center for Drug Evaluation and Research |archiveurl=http://web.archive.org/web/20070624223312/www.accessdata.fda.gov/scripts/cder/onctools/summary.cfm?ID=353 |archivedate=29 September 2007 }}</ref> In November 1996, the FDA also approved sargramostim for treatment of [[Fungal infection in animals|fungal infection]]s and replenishment of white blood cells following chemotherapy.<ref name="urlNewly Approved Drug Therapies (179): Leukine (sargramostim), Immunex">{{cite web| url = http://www.centerwatch.com/patient/drugs/dru179.html | title = Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex | author = | authorlink = | coauthors = | date = | work = | publisher = CenterWatch | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 12 October 2008}}</ref>


===Rheumatoid arthritis===
=== 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.<ref>{{cite web|url=http://www.drugdevelopment-technology.com/projects/mor103/ |title=MOR103 - Antibody for the Treatment of Rheumatoid Arthritis, Germany |year=2010 }}</ref>
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.<ref name="pmid23448220">{{cite journal | author = Deiß A, Brecht I, Haarmann A, Buttmann M | title = Treating multiple sclerosis with monoclonal antibodies: a 2013 update | journal = Expert Rev Neurother | volume = 13 | issue = 3 | pages = 313–35 | year = 2013 | pmid = 23448220 | doi = 10.1586/ern.13.17 }}</ref>


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


==References==
== References ==
{{Reflist}}
{{Reflist}}


==External links==
== External links ==
* [http://www.gm-csf.com/ Official gentaur web site]
* [http://www.gm-csf.com/ Official gentaur web site]
* [http://www.leukine.com/ Official Leukine web site]
* [http://www.leukine.com/ Official Leukine web site]
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{{PDB Gallery|geneid=1437}}
{{PDB Gallery|geneid=1437}}
{{Colony-stimulating factors}}
{{Colony-stimulating factors}}

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{{DEFAULTSORT:Granulocyte Macrophage Colony-Stimulating Factor}}
{{DEFAULTSORT:Granulocyte Macrophage Colony-Stimulating Factor}}

Revision as of 07:54, 17 August 2014

Not to be confused with granulocyte colony-stimulating factor.

Template:PBB

Granulocyte-macrophage colony-stimulating factor
three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor
Identifiers
SymbolGM_CSF
PfamPF01109
Pfam clanCL0053
InterProIPR000773
PROSITEPDOC00584
SCOP22gmf / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Granulocyte-macrophage colony-stimulating factor
Clinical data
ATC code
Identifiers
  • Human granulocyte macrophage colony stimulating factor
CAS Number
DrugBank
ChemSpider
Chemical and physical data
FormulaC639H1006N168O196S8
Molar mass14434.5 g/mol g·mol−1
 ☒NcheckY (what is this?)  (verify)

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

Functions

GM-CSF is a cytokine that functions as a white blood cell growth factor.[1] 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. GM-CSF signals via signal transducer and activator of transcription, STAT5.[2]

Genetic s

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.[3]

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 (Leukine). It is used as a medication to stimulate the production of white blood cells and thus prevent neutropenia following chemotherapy.[4]

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[5] 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.[6] 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.[7] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.[8]

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.[9]

See also

References

  1. ^ Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R (2014). "Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor". Med. Oncol. 31 (1): 774. doi:10.1007/s12032-013-0774-6. PMID 24264600.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Voehringer D (2012). "Basophil modulation by cytokine instruction". Eur. J. Immunol. 42 (10): 2544–50. doi:10.1002/eji.201142318. PMID 23042651.
  3. ^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)".
  4. ^ Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L (2013). "Trial Watch: Immunostimulatory cytokines". Oncoimmunology. 2 (7): e24850. doi:10.4161/onci.24850. PMC 3782010. PMID 24073369.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R, Pelusio A, Le Boeuf F, Burns J, Evgin L, De Silva N, Cvancic S, Robertson T, Je JE, Lee YS, Parato K, Diallo JS, Fenster A, Daneshmand M, Bell JC, Kirn DH (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature. 477 (7362): 99–102. doi:10.1038/nature10358. PMID 21886163.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ By HAROLD M. SCHMECK JrPublished: November 02, 1987 (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug - New York Times". Nytimes.com. Retrieved 2012-06-20.{{cite web}}: CS1 maint: numeric names: authors list (link)
  7. ^ "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. Retrieved 20 September 2009. {{cite web}}: |archive-date= / |archive-url= timestamp mismatch; 24 June 2007 suggested (help)
  8. ^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. Retrieved 12 October 2008. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  9. ^ Deiß A, Brecht I, Haarmann A, Buttmann M (2013). "Treating multiple sclerosis with monoclonal antibodies: a 2013 update". Expert Rev Neurother. 13 (3): 313–35. doi:10.1586/ern.13.17. PMID 23448220.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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