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Granulocyte macrophage colony-stimulating factor

granulocyte macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor (gm-csf)
1CSG, 2GMF, 4NKQ, 5C7X, 5D70, 5D71, 5D72, 4RS1

Identifiers Aliases CSF2, GMCSF, colony stimulating factor 2 External IDs MGI: 1339752 HomoloGene: 600 GeneCards: CSF2 RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez
Ensembl
UniProt
RefSeq mRNA

NM_000758

NM_009969

RefSeq protein

NP_000749

NP_034099

Location UCSC Chr 5: 13207 – 13208 Mb Chr 11: 5425 – 5425 Mb PubMed search 1 2 Wikidata
Granulocyte-macrophage colony-stimulating factor
three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor rhGM_CSF
Identifiers
Symbol GM_CSF
Pfam PF01109
Pfam clan CL0053
InterPro IPR000773
PROSITE PDOC00584
SCOP 2gmf
SUPERFAMILY 2gmf
Granulocyte macrophage colony-stimulating factor
Clinical data
ATC code
  • L03AA09 WHO
Identifiers
IUPAC name
CAS Number
  • 83869-56-1 Y
DrugBank
  • DB00020 N
ChemSpider
  • none
Chemical and physical data
Formula C639H1006N168O196S8
Molar mass 144345 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

Unlike granulocyte colony-stimulating factor, which specifically promotes neutrophil proliferation and maturation, GM-CSF affects more cell types, especially macrophages and eosinophils3

Contents

  • 1 Function
  • 2 Genetics
  • 3 Glycosylation
  • 4 Medical use
    • 41 Sargramostim
    • 42 Rheumatoid arthritis
  • 5 See also
  • 6 References
  • 7 External links

Functionedit

GM-CSF is a monomeric glycoprotein that functions as a cytokine - it is a white blood cell growth factor4 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 surface5

GM-CSF signals via signal transducer and activator of transcription, STAT56 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 toxicity7 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 tract8

Geneticsedit

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 139

Glycosylationedit

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

Medical useedit

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 chemotherapy10

GM-CSF has also been evaluated in clinical trials for its potential as a vaccine adjuvant in HIV-infected patients1112

Sargramostimedit

The sequence of human GM-CSF was first identified in 1985 and soon three recominbant human GM-CSFs were produced, one in bacteria, one in mammalian cells, and one in yeast;13 Immunex developed GM-CSF manufactured in yeast into sargramostim Leukine14 Clinical trials of sargramostim were initiated in 1987;15 in that same year it was administered to six people as part of a compassionate-use protocol for the victims of cesium irradiation from the Goiânia accident16

It was approved by the FDA in March 1991 under the trade name Leukine 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 disease17 In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy18 A liquid formulation was approved in 199514 Immunex was acquired by Amgen in 200215 As part of the acquisition, Leukine was spun off to Berlex, which became Bayer HealthCare in 200714 In 2009, Genzyme acquired the rights to Leukine from Bayer, including the manufacturing facility in the Seattle area151920

Rheumatoid arthritisedit

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-CSF21

See alsoedit

  • CFU-GM
  • Granulocyte macrophage colony-stimulating factor receptor
  • Filgrastim Neupogen, a granulocyte colony-stimulating factor G-CSF analog
  • Pegfilgrastim Neulasta, a PEGylated form filgrastim

Referencesedit

  1. ^ "Human PubMed Reference:" 
  2. ^ "Mouse PubMed Reference:" 
  3. ^ Root RK, Dale DC 1999 "Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: comparisons and potential for use in the treatment of infections in nonneutropenic patients" The Journal of Infectious Diseases 179 Suppl 2: S342–352 PMID 10081506 
  4. ^ Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R Jan 2014 "Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor" Medical Oncology 31 1: 774 PMID 24264600 doi:101007/s12032-013-0774-6 
  5. ^ Gasson JC Mar 1991 "Molecular physiology of granulocyte-macrophage colony-stimulating factor" Blood 77 6: 1131–45 PMID 2001448 
  6. ^ Voehringer D Oct 2012 "Basophil modulation by cytokine instruction" European Journal of Immunology 42 10: 2544–50 PMID 23042651 doi:101002/eji201142318 
  7. ^ Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS Oct 2013 "Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival" Immunity 39 4: 697–710 PMC 3841917  PMID 24138881 doi:101016/jimmuni201309006 
  8. ^ Hansen PJ, Dobbs KB, Denicol AC Sep 2014 "Programming of the preimplantation embryo by the embryokine colony stimulating factor 2" Animal Reproduction Science 149 1-2: 59–66 PMID 24954585 doi:101016/janireprosci201405017 
  9. ^ "Entrez Gene: CSF2 colony stimulating factor 2 granulocyte-macrophage" 
  10. ^ Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L Jul 2013 "Trial Watch: Immunostimulatory cytokines" Oncoimmunology 2 7: e24850 PMC 3782010  PMID 24073369 doi:104161/onci24850 
  11. ^ Hellerstein M, Xu Y, Marino T, Lu S, Yi H, Wright ER, Robinson HL Nov 2012 "Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine" Human Vaccines & Immunotherapeutics 8 11: 1654–8 PMC 3601140  PMID 23111169 doi:104161/hv21978 
  12. ^ Iyer SS, Amara RR 2014 "DNA/MVA Vaccines for HIV/AIDS" Vaccines 2 1: 160–78 PMC 4494194  PMID 26344473 doi:103390/vaccines2010160 
  13. ^ Armitage JO December 1998 "Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor" Blood 92 12: 4491–508 PMID 9845514 
  14. ^ a b c Staff May 2008 "Back to the Future: Original Liquid Leukine® Coming Soon" PDF Oncology Business Review 
  15. ^ a b c "Immunex Corporation" Company Histories & Profiles FundingUniversecom Retrieved 12 November 2011 
  16. ^ Schmeck HM 1987-11-02 "Radiation Team Sent to Brazil Saves Two With a New Drug" New York Times Retrieved 2012-06-20 
  17. ^ "Approval Summary for sargramostim" Oncology Tools US Food and Drug Administration, Center for Drug Evaluation and Research 1991-03-05 Archived from the original on 24 June 2007 Retrieved 20 September 2009 
  18. ^ "Newly Approved Drug Therapies 179: Leukine sargramostim, Immunex" CenterWatch Retrieved 2008-10-12 
  19. ^ "Bayer Healthcare Pharmaceuticals Plant, Snohomish County, Washington State" pharmaceutical-technologycom Retrieved 12 November 2011 
  20. ^ "Genzyme and Bayer HealthCare Enter New Strategic Agreement" Genzyme March 31, 2009 Retrieved 12 November 2011 
  21. ^ Deiß A, Brecht I, Haarmann A, Buttmann M Mar 2013 "Treating multiple sclerosis with monoclonal antibodies: a 2013 update" Expert Review of Neurotherapeutics 13 3: 313–35 PMID 23448220 doi:101586/ern1317 

External linksedit

  • Official gentaur web site
  • Official Leukine web site
  • Granulocyte-Macrophage Colony-Stimulating Factor at the US National Library of Medicine Medical Subject Headings MeSH
  • Molecular and cellular biology portal

granulocyte macrophage colony stimulating factor function, granulocyte macrophage colony-stimulating factor, granulocyte-macrophage colony stimulating factor ndf-rt, granulocyte-macrophage colony-stimulating factor (gm-csf)


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