Granulocyte colony-stimulating factor(G-CSForGCSF), also known ascolony-stimulating factor 3(CSF 3), is aglycoproteinthat stimulates thebone marrowto producegranulocytesandstem cellsand release them into thebloodstream.[5][6]
Functionally, it is acytokineandhormone,a type ofcolony-stimulating factor,and is produced by a number of differenttissues.Thepharmaceuticalanalogs of naturally occurring G-CSF are calledfilgrastimandlenograstim.
G-CSF also stimulates the survival, proliferation, differentiation, and function ofneutrophil precursorsand matureneutrophils.
Biological function
editG-CSF is produced byendothelium,macrophages,and a number of otherimmunecells. The natural human glycoprotein exists in two forms, a 174- and 177-amino-acid-longproteinof molecular weight 19,600 grams permole.The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products byrecombinant DNA(rDNA) technology.[citation needed]
- White blood cells
- TheG-CSF-receptoris present on precursor cells in thebone marrow,and, in response to stimulation by G-CSF, initiates proliferation anddifferentiationinto maturegranulocytes.G-CSF stimulates the survival, proliferation, differentiation, and function ofneutrophil precursorsand matureneutrophils.G-CSF regulates them usingJanus kinase (JAK)/signal transducer and activator of transcription (STAT)and Ras/mitogen-activated protein kinase(MAPK) andphosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signal transduction pathway.[citation needed]
- Hematopoietic System
- G-CSF is also a potent inducer ofhematopoietic stem cell(HSC) mobilization from the bone marrow into the bloodstream, although it has been shown that it does not directly affect the hematopoietic progenitors that are mobilized.[7]
- Neurons
- G-CSF can also act on neuronal cells as a neurotrophic factor. Indeed, its receptor is expressed by neurons in the brain and spinal cord. The action of G-CSF in the central nervous system is to induceneurogenesis,to increase theneuroplasticityand to counteractapoptosis.[8][9]These properties are currently under investigations for the development of treatments of neurological diseases such ascerebral ischemia.[citation needed]
Genetics
editThe gene for G-CSF is located onchromosome 17,locus q11.2-q12. Nagata et al. found that the GCSF gene has fourintrons,and that two differentpolypeptidesare synthesized from the same gene by differential splicing of mRNA.[10]
The two polypeptides differ by the presence or absence of three amino acids. Expression studies indicate that both have authentic GCSF activity.[citation needed]
It is thought that stability of the G-CSF mRNA is regulated by an RNA element called theG-CSF factor stem-loop destabilising element.[citation needed]
Medical use
editChemotherapy-induced neutropenia
editChemotherapy can causemyelosuppressionand unacceptably low levels ofwhite blood cells(leukopenia), making patients susceptible toinfectionsandsepsis.G-CSF stimulates the production ofgranulocytes,a type of white blood cell. Inoncologyandhematology,a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality fromneutropeniaafterchemotherapy,allowing higher-intensity treatment regimens.[11]It is administered to oncology patients via subcutaneous or intravenous routes.[12]A QSP model of neutrophil production and a PK/PD model of a cytotoxic chemotherapeutic drug (Zalypsis) have been developed to optimize the use of G-CSF in chemotherapy regimens with the aim to prevent mild-neutropenia.[13]
G-CSF was first trialled as a therapy for neutropenia induced by chemotherapy in 1988. The treatment was well tolerated and a dose-dependent rise in circulating neutrophils was noted.[14]
A study in mice has shown that G-CSF may decreasebone mineral density.[15]
G-CSF administration has been shown to attenuate thetelomereloss associated with chemotherapy.[16]
Use in drug-induced neutropenia
editNeutropeniacan be a severe side effect ofclozapine,anantipsychoticmedication in the treatment ofschizophrenia.G-CSF can restore neutrophil count. Following a return to baseline after stopping the drug, it may sometimes be safelyrechallengedwith the added use of G-CSF.[17][18]
Before blood donation
editG-CSF is also used to increase the number ofhematopoietic stem cellsin the blood of the donor before collection byleukapheresisfor use inhematopoietic stem cell transplantation.For this purpose, G-CSF appears to be safe inpregnancyduringimplantationas well as during thesecond and third trimesters.[19]Breastfeedingshould be withheld for three days after CSF administration to allow forclearanceof it from the milk.[19]People who have been administered colony-stimulating factors do not have a higher risk ofleukemiathan people who have not.[19]
Stem cell transplants
editG-CSF may also be given to the receiver inhematopoietic stem cell transplantation,to compensate forconditioning regimens.[16]
Side effect
editThe skin diseaseSweet's syndromeis a known side effect of using this drug.[20]
History
editMouse granulocyte-colony stimulating factor (G-CSF) was first recognised and purified inWalter and Eliza Hall Institute,Australiain 1983,[21]and the human form was cloned by groups fromJapanandGermany/United Statesin 1986.[10][22]
The FDA approved the firstbiosimilarof Neulasta in June 2018. It is made byMylanand sold as Fulphila.[23]
Pharmaceutical variants
editTherecombinanthuman G-CSF (rhG-CSF) synthesised in anE. coliexpression system is calledfilgrastim.The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim.[citation needed]
Filgrastim was first marketed byAmgenwith the brand nameNeupogen.Several bio-generic versions are now also available in markets such as Europe and Australia. Filgrastim (Neupogen) andPEG-filgrastim(Neulasta) are two commercially available forms of rhG-CSF. The PEG (polyethylene glycol) form has a much longerhalf-life,reducing the necessity of daily injections.
Another form of rhG-CSF calledlenograstimis synthesised inChinese hamster ovary cells(CHO cells). As this is a mammalian cell expression system, lenograstim is indistinguishable from the 174-amino acid natural human G-CSF. No clinical or therapeutic consequences of the differences between filgrastim and lenograstim have yet been identified, but there are no formal comparative studies.
Research
editG-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents.[24][25]
Mesoblastplanned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plusSDF(stromal cell-derived factor) directly to the heart.[26]
G-CSF has been shown to reduceinflammation,reduceamyloid betaburden, and reverse cognitive impairment in a mouse model ofAlzheimer's disease.[27]
Due to its neuroprotective properties, G-CSF is currently under investigation forcerebral ischemiain a clinical phase IIb[28]and several clinical pilot studies are published for other neurological disease such asamyotrophic lateral sclerosis[29]A combination of human G-CSF andcord bloodcells has been shown to reduce impairment from chronic traumatic brain injury in rats.[30]
See also
editReferences
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- ^abcGRCm38: Ensembl release 89: ENSMUSG00000038067–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^Tay J, Levesque JP, Winkler IG (February 2017)."Cellular players of hematopoietic stem cell mobilization in the bone marrow niche".International Journal of Hematology.105(2): 129–140.doi:10.1007/s12185-016-2162-4.PMID27943116.
- ^Thomas J, Liu F, Link DC (May 2002). "Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor".Current Opinion in Hematology.9(3): 183–189.doi:10.1097/00062752-200205000-00002.PMID11953662.S2CID5774130.
- ^Schneider A, Krüger C, Steigleder T, Weber D, Pitzer C, Laage R, et al. (August 2005)."The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis".The Journal of Clinical Investigation.115(8): 2083–2098.doi:10.1172/JCI23559.PMC1172228.PMID16007267.
- ^Pitzer C, Krüger C, Plaas C, Kirsch F, Dittgen T, Müller R, et al. (December 2008)."Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis".Brain.131(Pt 12): 3335–3347.doi:10.1093/brain/awn243.PMC2639207.PMID18835867.
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- ^Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, et al. (October 2013)."The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials".Annals of Oncology.24(10): 2475–2484.doi:10.1093/annonc/mdt226.PMC3841419.PMID23788754.
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- ^Hirbe AC, Uluçkan O, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, et al. (April 2007)."Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner".Blood.109(8): 3424–3431.doi:10.1182/blood-2006-09-048686.PMC1852257.PMID17192391.
- ^abSzyper-Kravitz M, Uziel O, Shapiro H, Radnay J, Katz T, Rowe JM, et al. (January 2003). "Granulocyte colony-stimulating factor administration upregulates telomerase activity in CD34+ haematopoietic cells and may prevent telomere attrition after chemotherapy".British Journal of Haematology.120(2): 329–336.doi:10.1046/j.1365-2141.2003.04043.x.PMID12542495.S2CID5785335.
- ^Myles N, Myles H, Clark SR, Bird R, Siskind D (October 2017)."Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations".The Australian and New Zealand Journal of Psychiatry.51(10): 980–989.doi:10.1177/0004867417720516.PMID28747065.
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- ^abcPessach I, Shimoni A, Nagler A (2013)."Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know?".Human Reproduction Update.19(3): 259–267.doi:10.1093/humupd/dms053.PMID23287427.
- ^Paydaş S, Sahin B, Seyrek E, Soylu M, Gonlusen G, Acar A, et al. (September 1993). "Sweet's syndrome associated with G-CSF".British Journal of Haematology.85(1): 191–192.doi:10.1111/j.1365-2141.1993.tb08668.x.PMID7504506.S2CID414133.
- ^Metcalf D (July 1985). "The granulocyte-macrophage colony-stimulating factors".Science.229(4708): 16–22.Bibcode:1985Sci...229...16M.doi:10.1126/science.2990035.PMID2990035.S2CID45170361.
- ^Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, et al. (April 1986). "Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells".Science.232(4746): 61–65.Bibcode:1986Sci...232...61S.doi:10.1126/science.2420009.PMID2420009.
- ^Office of the Commissioner (2019-09-11)."Press Announcements - FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment".fda.gov.
- ^Weisdorf D, Chao N, Waselenko JK, Dainiak N, Armitage JO, McNiece I, et al. (June 2006)."Acute radiation injury: contingency planning for triage, supportive care, and transplantation".Biology of Blood and Marrow Transplantation.12(6): 672–682.doi:10.1016/j.bbmt.2006.02.006.PMID16737941.
- ^Weinstock DM, Case C, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, et al. (June 2008)."Radiologic and nuclear events: contingency planning for hematologists/oncologists".Blood.111(12): 5440–5445.doi:10.1182/blood-2008-01-134817.PMC2424146.PMID18287516.
- ^Finkel E (2005).Stem cells: controversy on the frontiers of science.Crows Nest: ABC Books.ISBN978-0-7333-1248-9.
- ^Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, et al. (September 2009)."Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice".Neuroscience.163(1): 55–72.doi:10.1016/j.neuroscience.2009.05.071.PMC5966834.PMID19500657.
- ^"AXIS 2: AX200 for the Treatment of Ischemic Stroke - Full Text View - ClinicalTrials.gov".clinicaltrials.gov.
- ^Zhang Y, Wang L, Fu Y, Song H, Zhao H, Deng M, et al. (2009). "Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis".Amyotrophic Lateral Sclerosis.10(5–6): 430–431.doi:10.3109/17482960802588059.PMID19922135.S2CID43087598.
- ^Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, et al. (2014)."Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury".PLOS ONE.9(3): e90953.Bibcode:2014PLoSO...990953A.doi:10.1371/journal.pone.0090953.PMC3951247.PMID24621603.
Further reading
edit- Duarte RF, Frank DA (June 2002). "The synergy between stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF): molecular basis and clinical relevance".Leukemia & Lymphoma.43(6): 1179–1187.doi:10.1080/10428190290026231.PMID12152985.S2CID45748453.
- Mroczko B, Szmitkowski M (2005). "Hematopoietic cytokines as tumor markers".Clinical Chemistry and Laboratory Medicine.42(12): 1347–1354.doi:10.1515/CCLM.2004.253.PMID15576295.S2CID11414705.
- Sallerfors B, Olofsson T (October 1992). "Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays".European Journal of Haematology.49(4): 199–207.doi:10.1111/j.1600-0609.1992.tb00047.x.PMID1281454.S2CID35573524.
- Zink T, Ross A, Ambrosius D, Rudolph R, Holak TA (December 1992)."Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy".FEBS Letters.314(3): 435–439.Bibcode:1992FEBSL.314..435Z.doi:10.1016/0014-5793(92)81521-M.PMID1281794.S2CID28422738.
- Kubota N, Orita T, Hattori K, Oh-eda M, Ochi N, Yamazaki T (March 1990). "Structural characterization of natural and recombinant human granulocyte colony-stimulating factors".Journal of Biochemistry.107(3): 486–492.doi:10.1093/oxfordjournals.jbchem.a123072.PMID1692828.
- Nagata S, Tsuchiya M, Asano S, Yamamoto O, Hirata Y, Kubota N, et al. (March 1986)."The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor".The EMBO Journal.5(3): 575–581.doi:10.1002/j.1460-2075.1986.tb04249.x.PMC1166801.PMID2423327.
- Simmers RN, Smith J, Shannon MF, Wong G, Lopez AF, Baker E, et al. (February 1988). "Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia".Human Genetics.78(2): 134–136.doi:10.1007/BF00278182.PMID2448221.S2CID469736.
- Tweardy DJ, Cannizzaro LA, Palumbo AP, Shane S, Huebner K, Vantuinen P, et al. (August 1987). "Molecular cloning and characterization of a cDNA for human granulocyte colony-stimulating factor (G-CSF) from a glioblastoma multiforme cell line and localization of the G-CSF gene to chromosome band 17q21".Oncogene Research.1(3): 209–220.PMID2453015.
- Tsuchiya M, Nomura H, Asano S, Kaziro Y, Nagata S (March 1987)."Characterization of recombinant human granulocyte-colony-stimulating factor produced in mouse cells".The EMBO Journal.6(3): 611–616.doi:10.1002/j.1460-2075.1987.tb04798.x.PMC553441.PMID3034599.
- Devlin JJ, Devlin PE, Myambo K, Lilly MB, Rado TA, Warren MK (April 1987). "Expression of granulocyte colony-stimulating factor by human cell lines".Journal of Leukocyte Biology.41(4): 302–306.doi:10.1002/jlb.41.4.302.PMID3494801.S2CID26877622.
- Kanda N, Fukushige S, Murotsu T, Yoshida MC, Tsuchiya M, Asano S, et al. (November 1987). "Human gene coding for granulocyte-colony stimulating factor is assigned to the q21-q22 region of chromosome 17".Somatic Cell and Molecular Genetics.13(6): 679–684.doi:10.1007/BF01534488.PMID3499671.S2CID10909775.
- Le Beau MM, Lemons RS, Carrino JJ, Pettenati MJ, Souza LM, Diaz MO, et al. (December 1987). "Chromosomal localization of the human G-CSF gene to 17q11 proximal to the breakpoint of the t(15;17) in acute promyelocytic leukemia".Leukemia.1(12): 795–799.PMID3501046.
- Zink T, Ross A, Lüers K, Cieslar C, Rudolph R, Holak TA (July 1994). "Structure and dynamics of the human granulocyte colony-stimulating factor determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein".Biochemistry.33(28): 8453–8463.doi:10.1021/bi00194a009.PMID7518249.
- Corcione A, Baldi L, Zupo S, Dono M, Rinaldi GB, Roncella S, et al. (October 1994)."Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells".Journal of Immunology.153(7): 2868–2877.doi:10.4049/jimmunol.153.7.2868.PMID7522243.S2CID25302361.
- Watari K, Ozawa K, Tajika K, Tojo A, Tani K, Kamachi S, et al. (July 1994). "Production of human granulocyte colony stimulating factor by various kinds of stromal cells in vitro detected by enzyme immunoassay and in situ hybridization".Stem Cells.12(4): 416–423.doi:10.1002/stem.5530120409.PMID7524894.S2CID22671177.
- Hill CP, Osslund TD, Eisenberg D (June 1993)."The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors".Proceedings of the National Academy of Sciences of the United States of America.90(11): 5167–5171.Bibcode:1993PNAS...90.5167H.doi:10.1073/pnas.90.11.5167.PMC46676.PMID7685117.
- Haniu M, Horan T, Arakawa T, Le J, Katta V, Rohde MF (December 1995). "Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region".Archives of Biochemistry and Biophysics.324(2): 344–356.doi:10.1006/abbi.1995.0047.PMID8554326.
- McCracken S, Layton JE, Shorter SC, Starkey PM, Barlow DH, Mardon HJ (May 1996). "Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta".The Journal of Endocrinology.149(2): 249–258.doi:10.1677/joe.0.1490249.PMID8708536.
External links
edit- Granulocyte+Colony-Stimulating+Factorat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
- Overview of all the structural information available in thePDBforUniProt:P09919(Granulocyte colony-stimulating factor) at thePDBe-KB.
