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{{Short description|Mammalian protein found in humans}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{distinguish|granulocyte-macrophage colony-stimulating factor}} {{distinguish|granulocyte-macrophage colony-stimulating factor}}
{{Infobox_gene}} {{Infobox_gene}}


'''Granulocyte colony-stimulating factor''' ('''G-CSF''' or '''GCSF'''), also known as '''colony-stimulating factor 3''' ('''CSF 3'''), is a ] that stimulates the ] to produce ]s and ]s and release them into the ].<ref name="pmid25915812">{{cite journal | vauthors = Deotare U, Al-Dawsari G, Couban S, Lipton JH | title = G-CSF-primed bone marrow as a source of stem cells for allografting: revisiting the concept | journal = Bone Marrow Transplantation | volume = 50 | issue = 9 | pages = 1150–6 | date = September 2015 | pmid = 25915812 | doi = 10.1038/bmt.2015.80 | doi-access = free }}</ref><ref name="pmid27943116">{{cite journal | vauthors = Tay J, Levesque JP, Winkler IG | title = Cellular players of hematopoietic stem cell mobilization in the bone marrow niche | journal = International Journal of Hematology | date = December 2016 | pmid = 27943116 | doi = 10.1007/s12185-016-2162-4 | volume=105 | issue = 2 | pages=129–140| doi-access = free }}</ref> '''Granulocyte colony-stimulating factor''' ('''G-CSF''' or '''GCSF'''), also known as '''colony-stimulating factor 3''' ('''CSF 3'''), is a ] that stimulates the ] to produce ]s and ]s and release them into the ].<ref name="pmid25915812">{{cite journal | vauthors = Deotare U, Al-Dawsari G, Couban S, Lipton JH | title = G-CSF-primed bone marrow as a source of stem cells for allografting: revisiting the concept | journal = Bone Marrow Transplantation | volume = 50 | issue = 9 | pages = 1150–1156 | date = September 2015 | pmid = 25915812 | doi = 10.1038/bmt.2015.80 | s2cid = 20774089 | doi-access = }}</ref><ref name="pmid27943116">{{cite journal | vauthors = Tay J, Levesque JP, Winkler IG | title = Cellular players of hematopoietic stem cell mobilization in the bone marrow niche | journal = International Journal of Hematology | volume = 105 | issue = 2 | pages = 129–140 | date = February 2017 | pmid = 27943116 | doi = 10.1007/s12185-016-2162-4 | doi-access = free }}</ref>


Functionally, it is a ] and ], a type of ], and is produced by a number of different ]. The ] analogs of naturally occurring G-CSF are called ] and ]. Functionally, it is a ] and ], a type of ], and is produced by a number of different ]. The ] analogs of naturally occurring G-CSF are called ] and ].
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== Biological function == == Biological function ==
G-CSF is produced by ], ]s, and a number of other ] cells. The natural human glycoprotein exists in two forms, a 174- and 177-]-long ] of molecular weight 19,600&nbsp;grams per ]. The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by ] (rDNA) technology. G-CSF is produced by ], ]s, and a number of other ] cells. The natural human glycoprotein exists in two forms, a 174- and 177-]-long ] of molecular weight 19,600&nbsp;grams per ]. The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by ] (rDNA) technology.{{cn|date=February 2024}}


;White blood cells: The ] is present on precursor cells in the ], and, in response to stimulation by G-CSF, initiates proliferation and ] into mature ]s. G-CSF stimulates the survival, proliferation, differentiation, and function of ]s and mature ]s. G-CSF regulates them using ] and Ras/] (MAPK) and ] (PI3K)/] (Akt) signal transduction pathway. ;White blood cells: The ] is present on precursor cells in the ], and, in response to stimulation by G-CSF, initiates proliferation and ] into mature ]s. G-CSF stimulates the survival, proliferation, differentiation, and function of ]s and mature ]s. G-CSF regulates them using ] and Ras/] (MAPK) and ] (PI3K)/] (Akt) signal transduction pathway.{{cn|date=February 2024}}


;hematopoietic system: G-CSF is also a potent inducer of ] (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.<ref name="pmid11953662">{{cite journal | vauthors = Thomas J, Liu F, Link DC | title = Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor | journal = Current Opinion in Hematology | volume = 9 | issue = 3 | pages = 183–9 | date = May 2002 | pmid = 11953662 | doi = 10.1097/00062752-200205000-00002 | s2cid = 5774130 }}</ref> ;Hematopoietic System: G-CSF is also a potent inducer of ] (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.<ref name="pmid11953662">{{cite journal | vauthors = Thomas J, Liu F, Link DC | title = Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor | journal = Current Opinion in Hematology | volume = 9 | issue = 3 | pages = 183–189 | date = May 2002 | pmid = 11953662 | doi = 10.1097/00062752-200205000-00002 | s2cid = 5774130 }}</ref>


;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 induce ], to increase the ] and to counteract ].<ref name="pmid16007267">{{cite journal | vauthors = Schneider A, Krüger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassler N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A, Kuhn HG, Schäbitz WR | title = The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis | journal = The Journal of Clinical Investigation | volume = 115 | issue = 8 | pages = 2083–98 | date = August 2005 | pmid = 16007267 | pmc = 1172228 | doi = 10.1172/JCI23559 }}</ref><ref name="pmid18835867">{{cite journal | vauthors = Pitzer C, Krüger C, Plaas C, Kirsch F, Dittgen T, Müller R, Laage R, Kastner S, Suess S, Spoelgen R, Henriques A, Ehrenreich H, Schäbitz WR, Bach A, Schneider A | title = Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis | journal = Brain | volume = 131 | issue = Pt 12 | pages = 3335–47 | date = December 2008 | pmid = 18835867 | pmc = 2639207 | doi = 10.1093/brain/awn243 }}</ref> These properties are currently under investigations for the development of treatments of neurological diseases such as ]. ;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 induce ], to increase the ] and to counteract ].<ref name="pmid16007267">{{cite journal | vauthors = Schneider A, Krüger C, Steigleder T, Weber D, Pitzer C, Laage R, Aronowski J, Maurer MH, Gassler N, Mier W, Hasselblatt M, Kollmar R, Schwab S, Sommer C, Bach A, Kuhn HG, Schäbitz WR | title = The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis | journal = The Journal of Clinical Investigation | volume = 115 | issue = 8 | pages = 2083–2098 | date = August 2005 | pmid = 16007267 | pmc = 1172228 | doi = 10.1172/JCI23559 }}</ref><ref name="pmid18835867">{{cite journal | vauthors = Pitzer C, Krüger C, Plaas C, Kirsch F, Dittgen T, Müller R, Laage R, Kastner S, Suess S, Spoelgen R, Henriques A, Ehrenreich H, Schäbitz WR, Bach A, Schneider A | title = Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis | journal = Brain | volume = 131 | issue = Pt 12 | pages = 3335–3347 | date = December 2008 | pmid = 18835867 | pmc = 2639207 | doi = 10.1093/brain/awn243 }}</ref> These properties are currently under investigations for the development of treatments of neurological diseases such as ].{{cn|date=February 2024}}


==Genetics== ==Genetics==
The gene for G-CSF is located on ], locus q11.2-q12. Nagata et al. found that the GCSF gene has 4 ]s, and that 2 different ]s are synthesized from the same gene by differential splicing of mRNA.<ref name="pmid3484805"/> The gene for G-CSF is located on ], locus q11.2-q12. Nagata et al. found that the GCSF gene has four ]s, and that two different ]s are synthesized from the same gene by differential splicing of mRNA.<ref name="pmid3484805"/>
<!-- <ref name="N86">{{cite journal |vauthors=Nagata S, Tsuchiya M, Asano S, etal |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue=6052 |pages=415–8 |year=1986 |pmid=3484805 |doi=10.1038/319415a0}}</ref> --> <!-- <ref name="N86">{{cite journal |vauthors=Nagata S, Tsuchiya M, Asano S, etal |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue=6052 |pages=415–8 |year=1986 |pmid=3484805 |doi=10.1038/319415a0}}</ref> -->


The 2 polypeptides differ by the presence or absence of 3 amino acids. Expression studies indicate that both have authentic GCSF activity. The two polypeptides differ by the presence or absence of three amino acids. Expression studies indicate that both have authentic GCSF activity.{{cn|date=February 2024}}


It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the ]. It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the ].{{cn|date=February 2024}}


== Medical use == == Medical use ==
===Chemotherapy induced neutropenia === ===Chemotherapy-induced neutropenia===


Chemotherapy can cause ] and unacceptably low levels of ]s (]), making patients susceptible to ]s and ]. G-CSF stimulates the production of ]s, a type of white blood cell. In ] and ], a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality from ] after ], allowing higher-intensity treatment regimens.<ref name="pmid23788754">{{cite journal | vauthors = Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, Huang M, Crawford J | title = 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 | journal = Annals of Oncology | volume = 24 | issue = 10 | pages = 2475–84 | date = October 2013 | pmid = 23788754 | pmc = 3841419 | doi = 10.1093/annonc/mdt226 }}</ref> It is administered to oncology patients via subcutaneous or intravenous routes.<ref>{{cite web |url= http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/cancer-drugs/gcsf|title= Granulocyte colony stimulating factor (G-CSF)|website= Cancer Research UK |access-date= 12 November 2014}}</ref> 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.<ref>{{cite journal |last1=Craig |first1=Morgan |last2=Humphries |first2=Antony R |last3=Nekka |first3=Fahima |last4=Bélair |first4=Jacques |last5=Li |first5=Jun |last6=Mackey |first6=Michael C |title=Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia |journal=Journal of Theoretical Biology |volume=385 |pages=77–89 |date = 21 November 2015 |doi=10.1016/j.jtbi.2015.08.015 |pmid=26343861 }}</ref> Chemotherapy can cause ] and unacceptably low levels of ]s (]), making patients susceptible to ]s and ]. G-CSF stimulates the production of ]s, a type of white blood cell. In ] and ], a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality from ] after ], allowing higher-intensity treatment regimens.<ref name="pmid23788754">{{cite journal | vauthors = Lyman GH, Dale DC, Culakova E, Poniewierski MS, Wolff DA, Kuderer NM, Huang M, Crawford J | title = 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 | journal = Annals of Oncology | volume = 24 | issue = 10 | pages = 2475–2484 | date = October 2013 | pmid = 23788754 | pmc = 3841419 | doi = 10.1093/annonc/mdt226 }}</ref> It is administered to oncology patients via subcutaneous or intravenous routes.<ref>{{cite web |url= http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/cancer-drugs/gcsf|title= Granulocyte colony stimulating factor (G-CSF)|website= Cancer Research UK |access-date= 12 November 2014}}</ref> 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.<ref>{{cite journal | vauthors = Craig M, Humphries AR, Nekka F, Bélair J, Li J, Mackey MC | title = Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia | journal = Journal of Theoretical Biology | volume = 385 | pages = 77–89 | date = November 2015 | pmid = 26343861 | doi = 10.1016/j.jtbi.2015.08.015 | bibcode = 2015JThBi.385...77C }}</ref>


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.<ref>{{cite journal | vauthors = Morstyn G, Campbell L, Souza LM, Alton NK, Keech J, Green M, Sheridan W, Metcalf D, Fox R | s2cid = 21255495 | title = Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy | journal = Lancet | volume = 1 | issue = 8587 | pages = 667–72 | date = March 1988 | pmid = 2895212 | doi = 10.1016/S0140-6736(88)91475-4 }}</ref> 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.<ref>{{cite journal | vauthors = Morstyn G, Campbell L, Souza LM, Alton NK, Keech J, Green M, Sheridan W, Metcalf D, Fox R | title = Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy | journal = Lancet | volume = 1 | issue = 8587 | pages = 667–672 | date = March 1988 | pmid = 2895212 | doi = 10.1016/S0140-6736(88)91475-4 | s2cid = 21255495 }}</ref>


A study in mice has shown that G-CSF may decrease ].<ref name="pmid17192391">{{cite journal | vauthors = Hirbe AC, Uluçkan O, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, Trinkaus K, Apicelli A, Weilbaecher K | title = Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner | journal = Blood | volume = 109 | issue = 8 | pages = 3424–31 | date = April 2007 | pmid = 17192391 | pmc = 1852257 | doi = 10.1182/blood-2006-09-048686 }}</ref> A study in mice has shown that G-CSF may decrease ].<ref name="pmid17192391">{{cite journal | vauthors = Hirbe AC, Uluçkan O, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, Trinkaus K, Apicelli A, Weilbaecher K | title = Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner | journal = Blood | volume = 109 | issue = 8 | pages = 3424–3431 | date = April 2007 | pmid = 17192391 | pmc = 1852257 | doi = 10.1182/blood-2006-09-048686 }}</ref>


G-CSF administration has been shown to attenuate the ] loss associated with chemotherapy.<ref name="pmid12542495">{{cite journal | vauthors = Szyper-Kravitz M, Uziel O, Shapiro H, Radnay J, Katz T, Rowe JM, Lishner M, Lahav M | title = Granulocyte colony-stimulating factor administration upregulates telomerase activity in CD34+ haematopoietic cells and may prevent telomere attrition after chemotherapy | journal = British Journal of Haematology | volume = 120 | issue = 2 | pages = 329–36 | date = January 2003 | pmid = 12542495 | doi = 10.1046/j.1365-2141.2003.04043.x | s2cid = 5785335 | doi-access = free }}</ref> G-CSF administration has been shown to attenuate the ] loss associated with chemotherapy.<ref name="pmid12542495">{{cite journal | vauthors = Szyper-Kravitz M, Uziel O, Shapiro H, Radnay J, Katz T, Rowe JM, Lishner M, Lahav M | title = Granulocyte colony-stimulating factor administration upregulates telomerase activity in CD34+ haematopoietic cells and may prevent telomere attrition after chemotherapy | journal = British Journal of Haematology | volume = 120 | issue = 2 | pages = 329–336 | date = January 2003 | pmid = 12542495 | doi = 10.1046/j.1365-2141.2003.04043.x | s2cid = 5785335 | doi-access = }}</ref>


===Use in drug-induced neutropenia=== ===Use in drug-induced neutropenia===
] can be a severe side effect of ], an ] medication in the treatment of ]. G-CSF can restore neutrophil count. Following a return to baseline after stopping the drug, it may sometimes be safely ] with the added use of G-CSF.<ref name="Myles">{{cite journal | vauthors = Myles N | title = Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations. |journal = The Australian and New Zealand Journal of Psychiatry | date = October 2017 |volume = 51 | issue = 10 | pages = 980–989 |doi = 10.1177/0004867417720516 | pmid = 28747065| doi-access = free }}</ref><ref name="Lally">{{cite journal | vauthors = Lally J | title = The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review. | journal = Journal of Clinical Psychopharmacology | date = October 2017 | volume = 37 | issue = 5 | pages = 600–604 | doi = 10.1097/JCP.0000000000000767 | pmid = 28817489| s2cid = 41269943 | url = https://kclpure.kcl.ac.uk/portal/en/publications/the-use-of-granulocyte-colonystimulating-factor-in-clozapine-rechallenge(4468e274-9be2-4117-81e2-2b79c1afe1be).html }}</ref> ] can be a severe side effect of ], an ] medication in the treatment of ]. G-CSF can restore neutrophil count. Following a return to baseline after stopping the drug, it may sometimes be safely ] with the added use of G-CSF.<ref name="Myles">{{cite journal | vauthors = Myles N, Myles H, Clark SR, Bird R, Siskind D | title = Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations | journal = The Australian and New Zealand Journal of Psychiatry | volume = 51 | issue = 10 | pages = 980–989 | date = October 2017 | pmid = 28747065 | doi = 10.1177/0004867417720516 | doi-access = free }}</ref><ref name="Lally">{{cite journal | vauthors = Lally J, Malik S, Krivoy A, Whiskey E, Taylor DM, Gaughran FP, Flanagan RJ, Mijovic A, MacCabe JH | title = The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review | journal = Journal of Clinical Psychopharmacology | volume = 37 | issue = 5 | pages = 600–604 | date = October 2017 | pmid = 28817489 | doi = 10.1097/JCP.0000000000000767 | s2cid = 41269943 | url = https://kclpure.kcl.ac.uk/portal/en/publications/ca7cfadf-aa22-4c06-ae6d-a8fcce079c12 }}</ref>


===Before blood donation=== ===Before blood donation===
G-CSF is also used to increase the number of ] in the blood of the donor before collection by ] for use in ]. For this purpose, G-CSF appears to be safe in ] during ] as well as during the ].<ref name=Pessach2013>{{cite journal | vauthors = Pessach I, Shimoni A, Nagler A | title = Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know? | journal = Human Reproduction Update | volume = 19 | issue = 3 | pages = 259–67 | year = 2013 | pmid = 23287427 | doi = 10.1093/humupd/dms053 | doi-access = free }}</ref> ] should be withheld for 3 days after CSF administration to allow for ] of it from the milk.<ref name=Pessach2013/> People who have been administered colony-stimulating factors do not have a higher risk of ] than people who have not.<ref name=Pessach2013/> G-CSF is also used to increase the number of ] in the blood of the donor before collection by ] for use in ]. For this purpose, G-CSF appears to be safe in ] during ] as well as during the ].<ref name=Pessach2013>{{cite journal | vauthors = Pessach I, Shimoni A, Nagler A | title = Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know? | journal = Human Reproduction Update | volume = 19 | issue = 3 | pages = 259–267 | year = 2013 | pmid = 23287427 | doi = 10.1093/humupd/dms053 | doi-access = free }}</ref> ] should be withheld for three days after CSF administration to allow for ] of it from the milk.<ref name=Pessach2013/> People who have been administered colony-stimulating factors do not have a higher risk of ] than people who have not.<ref name=Pessach2013/>


===Stem cell transplants=== ===Stem cell transplants===
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==Side effect== ==Side effect==
The skin disease ] is a known side effect of using this drug.<ref name="pmid7504506">{{cite journal | vauthors = Paydaş S, Sahin B, Seyrek E, Soylu M, Gonlusen G, Acar A, Tuncer I | title = Sweet's syndrome associated with G-CSF | journal = British Journal of Haematology | volume = 85 | issue = 1 | pages = 191–2 | date = September 1993 | pmid = 7504506 | doi = 10.1111/j.1365-2141.1993.tb08668.x | s2cid = 414133 }}</ref> The skin disease ] is a known side effect of using this drug.<ref name="pmid7504506">{{cite journal | vauthors = Paydaş S, Sahin B, Seyrek E, Soylu M, Gonlusen G, Acar A, Tuncer I | title = Sweet's syndrome associated with G-CSF | journal = British Journal of Haematology | volume = 85 | issue = 1 | pages = 191–192 | date = September 1993 | pmid = 7504506 | doi = 10.1111/j.1365-2141.1993.tb08668.x | s2cid = 414133 }}</ref>


== History == == History ==
Mouse granulocyte-colony stimulating factor (G-CSF) was first recognised and purified in ], ] in 1983,<ref name="pmid2990035">{{cite journal | vauthors = Metcalf D | title = The granulocyte-macrophage colony-stimulating factors | journal = Science | volume = 229 | issue = 4708 | pages = 16–22 | date = July 1985 | pmid = 2990035 | doi = 10.1126/science.2990035 | bibcode = 1985Sci...229...16M }}</ref> and the human form was cloned by groups from ] and ]/] in 1986.<ref name="pmid3484805">{{cite journal | vauthors = Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H | s2cid = 4325026 | title = Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor | journal = Nature | volume = 319 | issue = 6052 | pages = 415–8 | year = 1986 | pmid = 3484805 | doi = 10.1038/319415a0 | bibcode = 1986Natur.319..415N }}</ref><ref name="pmid2420009">{{cite journal | vauthors = Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK | title = Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells | journal = Science | volume = 232 | issue = 4746 | pages = 61–5 | date = April 1986 | pmid = 2420009 | doi = 10.1126/science.2420009 | bibcode = 1986Sci...232...61S }}</ref> Mouse granulocyte-colony stimulating factor (G-CSF) was first recognised and purified in ], ] in 1983,<ref name="pmid2990035">{{cite journal | vauthors = Metcalf D | title = The granulocyte-macrophage colony-stimulating factors | journal = Science | volume = 229 | issue = 4708 | pages = 16–22 | date = July 1985 | pmid = 2990035 | doi = 10.1126/science.2990035 | s2cid = 45170361 | bibcode = 1985Sci...229...16M }}</ref> and the human form was cloned by groups from ] and ]/] in 1986.<ref name="pmid3484805">{{cite journal | vauthors = Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H | title = Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor | journal = Nature | volume = 319 | issue = 6052 | pages = 415–418 | year = 1986 | pmid = 3484805 | doi = 10.1038/319415a0 | s2cid = 4325026 | bibcode = 1986Natur.319..415N }}</ref><ref name="pmid2420009">{{cite journal | vauthors = Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK, Barendt J, Platzer E, Moore MA, Mertelsmann R, Welte K | title = Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells | journal = Science | volume = 232 | issue = 4746 | pages = 61–65 | date = April 1986 | pmid = 2420009 | doi = 10.1126/science.2420009 | bibcode = 1986Sci...232...61S }}</ref>

The FDA approved the first ] of Neulasta in June 2018. It is made by ] and sold as Fulphila.<ref>{{cite web |last1=Commissioner |first1=Office of the |title=Press Announcements - FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609805.htm |website=www.fda.gov |language=en|date=2019-09-11 }}</ref> The FDA approved the first ] of Neulasta in June 2018. It is made by ] and sold as Fulphila.<ref>{{cite web | author = Office of the Commissioner |title=Press Announcements - FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609805.htm |website=www.fda.gov |language=en|date=2019-09-11 }}</ref>


==Pharmaceutical variants== ==Pharmaceutical variants==
The ] human G-CSF (rhG-CSF) synthesised in an '']'' expression system is called ]. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim. The ] human G-CSF (rhG-CSF) synthesised in an '']'' expression system is called ]. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim.{{cn|date=February 2024}}


Filgrastim was first marketed by ] with the brand name ]. Several bio-generic versions are now also available in markets such as Europe and Australia. Filgrastim (Neupogen) and ] (Neulasta) are two commercially available forms of rhG-CSF. The PEG (]) form has a much longer ], reducing the necessity of daily injections. Filgrastim was first marketed by ] with the brand name ]. Several bio-generic versions are now also available in markets such as Europe and Australia. Filgrastim (Neupogen) and ] (Neulasta) are two commercially available forms of rhG-CSF. The PEG (]) form has a much longer ], reducing the necessity of daily injections.


Another form of rhG-CSF called ] is synthesised in ]s (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. Another form of rhG-CSF called ] is synthesised in ]s (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=== ===Research===
G-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents.<ref>{{cite journal | vauthors = Weisdorf D, Chao N, Waselenko JK, Dainiak N, Armitage JO, McNiece I, Confer D | title = Acute radiation injury: contingency planning for triage, supportive care, and transplantation | journal = Biology of Blood and Marrow Transplantation | volume = 12 | issue = 6 | pages = 672–82 | date = June 2006 | pmid = 16737941 | doi = 10.1016/j.bbmt.2006.02.006 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Weinstock DM, Case C, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, Weisdorf DJ, Confer DL | title = Radiologic and nuclear events: contingency planning for hematologists/oncologists | journal = Blood | volume = 111 | issue = 12 | pages = 5440–5 | date = June 2008 | pmid = 18287516 | pmc = 2424146 | doi = 10.1182/blood-2008-01-134817 }}</ref> G-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents.<ref>{{cite journal | vauthors = Weisdorf D, Chao N, Waselenko JK, Dainiak N, Armitage JO, McNiece I, Confer D | title = Acute radiation injury: contingency planning for triage, supportive care, and transplantation | journal = Biology of Blood and Marrow Transplantation | volume = 12 | issue = 6 | pages = 672–682 | date = June 2006 | pmid = 16737941 | doi = 10.1016/j.bbmt.2006.02.006 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Weinstock DM, Case C, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, Weisdorf DJ, Confer DL | title = Radiologic and nuclear events: contingency planning for hematologists/oncologists | journal = Blood | volume = 111 | issue = 12 | pages = 5440–5445 | date = June 2008 | pmid = 18287516 | pmc = 2424146 | doi = 10.1182/blood-2008-01-134817 }}</ref>


] planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus ] (stromal cell-derived factor) directly to the heart.<ref name="isbn0-7333-1248-9">{{cite book | last = Finkel | first = Elizabeth | name-list-style = vanc | title = Stem cells: controversy on the frontiers of science | publisher = ABC Books | location = Crows Nest | year = 2005 | isbn = 978-0-7333-1248-9 }}</ref> ] planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus ] (stromal cell-derived factor) directly to the heart.<ref name="isbn0-7333-1248-9">{{cite book | vauthors = Finkel E | title = Stem cells: controversy on the frontiers of science | publisher = ABC Books | location = Crows Nest | year = 2005 | isbn = 978-0-7333-1248-9 }}</ref>


G-CSF has been shown to reduce ], reduce ] burden, and reverse cognitive impairment in a mouse model of ].<ref name="pmid19500657">{{cite journal | vauthors = Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, Cao C, Arendash GW | title = Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice | journal = Neuroscience | volume = 163 | issue = 1 | pages = 55–72 | date = September 2009 | pmid = 19500657 | pmc = 5966834 | doi = 10.1016/j.neuroscience.2009.05.071 }}</ref> G-CSF has been shown to reduce ], reduce ] burden, and reverse cognitive impairment in a mouse model of ].<ref name="pmid19500657">{{cite journal | vauthors = Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, Cao C, Arendash GW | title = Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice | journal = Neuroscience | volume = 163 | issue = 1 | pages = 55–72 | date = September 2009 | pmid = 19500657 | pmc = 5966834 | doi = 10.1016/j.neuroscience.2009.05.071 }}</ref>


Due to its neuroprotective properties, G-CSF is currently under investigation for ] in a clinical phase IIb <ref>{{cite web|url=http://clinicaltrials.gov/ct/show/NCT00927836|title=AXIS 2: AX200 for the Treatment of Ischemic Stroke - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov}}</ref> and several clinical pilot studies are published for other neurological disease such as ]<ref name="pmid19922135">{{cite journal | vauthors = Zhang Y, Wang L, Fu Y, Song H, Zhao H, Deng M, Zhang J, Fan D | title = Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis | journal = Amyotrophic Lateral Sclerosis | volume = 10 | issue = 5–6 | pages = 430–1 | year = 2009 | pmid = 19922135 | doi = 10.3109/17482960802588059 | s2cid = 43087598 }}</ref> A combination of human G-CSF and ] cells has been shown to reduce impairment from chronic traumatic brain injury in rats.<ref name="pmid24621603">{{cite journal | vauthors = Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, Song S, Kaneko Y, Borlongan CV | title = 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 | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e90953 | year = 2014 | pmid = 24621603 | pmc = 3951247 | doi = 10.1371/journal.pone.0090953 | bibcode = 2014PLoSO...990953A }}</ref> Due to its neuroprotective properties, G-CSF is currently under investigation for ] in a clinical phase IIb <ref>{{cite web|url=http://clinicaltrials.gov/ct/show/NCT00927836|title=AXIS 2: AX200 for the Treatment of Ischemic Stroke - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov}}</ref> and several clinical pilot studies are published for other neurological disease such as ]<ref name="pmid19922135">{{cite journal | vauthors = Zhang Y, Wang L, Fu Y, Song H, Zhao H, Deng M, Zhang J, Fan D | title = Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis | journal = Amyotrophic Lateral Sclerosis | volume = 10 | issue = 5–6 | pages = 430–431 | year = 2009 | pmid = 19922135 | doi = 10.3109/17482960802588059 | s2cid = 43087598 }}</ref> A combination of human G-CSF and ] cells has been shown to reduce impairment from chronic traumatic brain injury in rats.<ref name="pmid24621603">{{cite journal | vauthors = Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, Song S, Kaneko Y, Borlongan CV | title = 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 | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e90953 | year = 2014 | pmid = 24621603 | pmc = 3951247 | doi = 10.1371/journal.pone.0090953 | doi-access = free | bibcode = 2014PLoSO...990953A }}</ref>


== See also == == See also ==
Line 77: Line 79:
== Further reading == == Further reading ==
{{refbegin | 2}} {{refbegin | 2}}
* {{cite journal | vauthors = Duarte RF, Franf DA | title = The synergy between stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF): molecular basis and clinical relevance | journal = Leukemia & Lymphoma | volume = 43 | issue = 6 | pages = 1179–87 | date = June 2002 | pmid = 12152985 | doi = 10.1080/10428190290026231 | s2cid = 45748453 }} * {{cite journal | vauthors = Duarte RF, Frank DA | title = The synergy between stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF): molecular basis and clinical relevance | journal = Leukemia & Lymphoma | volume = 43 | issue = 6 | pages = 1179–1187 | date = June 2002 | pmid = 12152985 | doi = 10.1080/10428190290026231 | s2cid = 45748453 }}
* {{cite journal | vauthors = Mroczko B, Szmitkowski M | s2cid = 11414705 | title = Hematopoietic cytokines as tumor markers | journal = Clinical Chemistry and Laboratory Medicine | volume = 42 | issue = 12 | pages = 1347–54 | year = 2005 | pmid = 15576295 | doi = 10.1515/CCLM.2004.253 }} * {{cite journal | vauthors = Mroczko B, Szmitkowski M | title = Hematopoietic cytokines as tumor markers | journal = Clinical Chemistry and Laboratory Medicine | volume = 42 | issue = 12 | pages = 1347–1354 | year = 2005 | pmid = 15576295 | doi = 10.1515/CCLM.2004.253 | s2cid = 11414705 }}
* {{cite journal | vauthors = Sallerfors B, Olofsson T | title = Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays | journal = European Journal of Haematology | volume = 49 | issue = 4 | pages = 199–207 | date = October 1992 | pmid = 1281454 | doi = 10.1111/j.1600-0609.1992.tb00047.x | s2cid = 35573524 }} * {{cite journal | vauthors = Sallerfors B, Olofsson T | title = Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays | journal = European Journal of Haematology | volume = 49 | issue = 4 | pages = 199–207 | date = October 1992 | pmid = 1281454 | doi = 10.1111/j.1600-0609.1992.tb00047.x | s2cid = 35573524 }}
* {{cite journal | vauthors = Zink T, Ross A, Ambrosius D, Rudolph R, Holak TA | title = Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy | journal = FEBS Letters | volume = 314 | issue = 3 | pages = 435–9 | date = December 1992 | pmid = 1281794 | doi = 10.1016/0014-5793(92)81521-M | s2cid = 28422738 | doi-access = free }} * {{cite journal | vauthors = Zink T, Ross A, Ambrosius D, Rudolph R, Holak TA | title = Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy | journal = FEBS Letters | volume = 314 | issue = 3 | pages = 435–439 | date = December 1992 | pmid = 1281794 | doi = 10.1016/0014-5793(92)81521-M | s2cid = 28422738 | doi-access = free | bibcode = 1992FEBSL.314..435Z }}
* {{cite journal | vauthors = Kubota N, Orita T, Hattori K, Oh-eda M, Ochi N, Yamazaki T | title = Structural characterization of natural and recombinant human granulocyte colony-stimulating factors | journal = Journal of Biochemistry | volume = 107 | issue = 3 | pages = 486–92 | date = March 1990 | pmid = 1692828 | doi = 10.1093/oxfordjournals.jbchem.a123072}} * {{cite journal | vauthors = Kubota N, Orita T, Hattori K, Oh-eda M, Ochi N, Yamazaki T | title = Structural characterization of natural and recombinant human granulocyte colony-stimulating factors | journal = Journal of Biochemistry | volume = 107 | issue = 3 | pages = 486–492 | date = March 1990 | pmid = 1692828 | doi = 10.1093/oxfordjournals.jbchem.a123072 }}
* {{cite journal | vauthors = Nagata S, Tsuchiya M, Asano S, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Yamazaki T | title = The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor | journal = The EMBO Journal | volume = 5 | issue = 3 | pages = 575–81 | date = March 1986 | pmid = 2423327 | pmc = 1166801 | doi = 10.1002/j.1460-2075.1986.tb04249.x}} * {{cite journal | vauthors = Nagata S, Tsuchiya M, Asano S, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Yamazaki T | title = The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor | journal = The EMBO Journal | volume = 5 | issue = 3 | pages = 575–581 | date = March 1986 | pmid = 2423327 | pmc = 1166801 | doi = 10.1002/j.1460-2075.1986.tb04249.x }}
* {{cite journal | vauthors = Simmers RN, Smith J, Shannon MF, Wong G, Lopez AF, Baker E, Sutherland GR, Vadas MA | s2cid = 469736 | title = Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia | journal = Human Genetics | volume = 78 | issue = 2 | pages = 134–6 | date = February 1988 | pmid = 2448221 | doi = 10.1007/BF00278182 }} * {{cite journal | vauthors = Simmers RN, Smith J, Shannon MF, Wong G, Lopez AF, Baker E, Sutherland GR, Vadas MA | title = Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia | journal = Human Genetics | volume = 78 | issue = 2 | pages = 134–136 | date = February 1988 | pmid = 2448221 | doi = 10.1007/BF00278182 | s2cid = 469736 | authorlink7 = Grant Robert Sutherland }}
* {{cite journal | vauthors = Tweardy DJ, Cannizzaro LA, Palumbo AP, Shane S, Huebner K, Vantuinen P, Ledbetter DH, Finan JB, Nowell PC, Rovera G | title = 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 | journal = Oncogene Research | volume = 1 | issue = 3 | pages = 209–20 | date = August 1987 | pmid = 2453015 }} * {{cite journal | vauthors = Tweardy DJ, Cannizzaro LA, Palumbo AP, Shane S, Huebner K, Vantuinen P, Ledbetter DH, Finan JB, Nowell PC, Rovera G | title = 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 | journal = Oncogene Research | volume = 1 | issue = 3 | pages = 209–220 | date = August 1987 | pmid = 2453015 }}
* {{cite journal | vauthors = Tsuchiya M, Nomura H, Asano S, Kaziro Y, Nagata S | title = Characterization of recombinant human granulocyte-colony-stimulating factor produced in mouse cells | journal = The EMBO Journal | volume = 6 | issue = 3 | pages = 611–6 | date = March 1987 | pmid = 3034599 | pmc = 553441 | doi = 10.1002/j.1460-2075.1987.tb04798.x}} * {{cite journal | vauthors = Tsuchiya M, Nomura H, Asano S, Kaziro Y, Nagata S | title = Characterization of recombinant human granulocyte-colony-stimulating factor produced in mouse cells | journal = The EMBO Journal | volume = 6 | issue = 3 | pages = 611–616 | date = March 1987 | pmid = 3034599 | pmc = 553441 | doi = 10.1002/j.1460-2075.1987.tb04798.x }}
<!-- cited inline * {{cite journal |vauthors=Nagata S, Tsuchiya M, Asano S, etal |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue= 6052 |pages= 415–8 |year= 1986 |pmid= 3484805 |doi= 10.1038/319415a0 }} --> <!-- cited inline * {{cite journal |vauthors=Nagata S, Tsuchiya M, Asano S, etal |title=Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor |journal=Nature |volume=319 |issue= 6052 |pages= 415–8 |year= 1986 |pmid= 3484805 |doi= 10.1038/319415a0 }} -->
* {{cite journal | vauthors = Devlin JJ, Devlin PE, Myambo K, Lilly MB, Rado TA, Warren MK | title = Expression of granulocyte colony-stimulating factor by human cell lines | journal = Journal of Leukocyte Biology | volume = 41 | issue = 4 | pages = 302–6 | date = April 1987 | pmid = 3494801 | doi = 10.1002/jlb.41.4.302| s2cid = 26877622 }} * {{cite journal | vauthors = Devlin JJ, Devlin PE, Myambo K, Lilly MB, Rado TA, Warren MK | title = Expression of granulocyte colony-stimulating factor by human cell lines | journal = Journal of Leukocyte Biology | volume = 41 | issue = 4 | pages = 302–306 | date = April 1987 | pmid = 3494801 | doi = 10.1002/jlb.41.4.302 | s2cid = 26877622 }}
* {{cite journal | vauthors = Kanda N, Fukushige S, Murotsu T, Yoshida MC, Tsuchiya M, Asano S, Kaziro Y, Nagata S | s2cid = 10909775 | title = Human gene coding for granulocyte-colony stimulating factor is assigned to the q21-q22 region of chromosome 17 | journal = Somatic Cell and Molecular Genetics | volume = 13 | issue = 6 | pages = 679–84 | date = November 1987 | pmid = 3499671 | doi = 10.1007/BF01534488 }} * {{cite journal | vauthors = Kanda N, Fukushige S, Murotsu T, Yoshida MC, Tsuchiya M, Asano S, Kaziro Y, Nagata S | title = Human gene coding for granulocyte-colony stimulating factor is assigned to the q21-q22 region of chromosome 17 | journal = Somatic Cell and Molecular Genetics | volume = 13 | issue = 6 | pages = 679–684 | date = November 1987 | pmid = 3499671 | doi = 10.1007/BF01534488 | s2cid = 10909775 }}
* {{cite journal | vauthors = Le Beau MM, Lemons RS, Carrino JJ, Pettenati MJ, Souza LM, Diaz MO, Rowley JD | title = Chromosomal localization of the human G-CSF gene to 17q11 proximal to the breakpoint of the t(15;17) in acute promyelocytic leukemia | journal = Leukemia | volume = 1 | issue = 12 | pages = 795–9 | date = December 1987 | pmid = 3501046 }} * {{cite journal | vauthors = Le Beau MM, Lemons RS, Carrino JJ, Pettenati MJ, Souza LM, Diaz MO, Rowley JD | title = Chromosomal localization of the human G-CSF gene to 17q11 proximal to the breakpoint of the t(15;17) in acute promyelocytic leukemia | journal = Leukemia | volume = 1 | issue = 12 | pages = 795–799 | date = December 1987 | pmid = 3501046 }}
* {{cite journal | vauthors = Zink T, Ross A, Lüers K, Cieslar C, Rudolph R, Holak TA | title = Structure and dynamics of the human granulocyte colony-stimulating factor determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein | journal = Biochemistry | volume = 33 | issue = 28 | pages = 8453–63 | date = July 1994 | pmid = 7518249 | doi = 10.1021/bi00194a009 }} * {{cite journal | vauthors = Zink T, Ross A, Lüers K, Cieslar C, Rudolph R, Holak TA | title = Structure and dynamics of the human granulocyte colony-stimulating factor determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein | journal = Biochemistry | volume = 33 | issue = 28 | pages = 8453–8463 | date = July 1994 | pmid = 7518249 | doi = 10.1021/bi00194a009 }}
* {{cite journal | vauthors = Corcione A, Baldi L, Zupo S, Dono M, Rinaldi GB, Roncella S, Taborelli G, Truini M, Ferrarini M, Pistoia V | title = Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells | journal = Journal of Immunology | volume = 153 | issue = 7 | pages = 2868–77 | date = October 1994 | pmid = 7522243 }} * {{cite journal | vauthors = Corcione A, Baldi L, Zupo S, Dono M, Rinaldi GB, Roncella S, Taborelli G, Truini M, Ferrarini M, Pistoia V | title = Spontaneous production of granulocyte colony-stimulating factor in vitro by human B-lineage lymphocytes is a distinctive marker of germinal center cells | journal = Journal of Immunology | volume = 153 | issue = 7 | pages = 2868–2877 | date = October 1994 | pmid = 7522243 | doi = 10.4049/jimmunol.153.7.2868 | s2cid = 25302361 | doi-access = free }}
* {{cite journal | vauthors = Watari K, Ozawa K, Tajika K, Tojo A, Tani K, Kamachi S, Harigaya K, Takahashi T, Sekiguchi S, Nagata S | title = Production of human granulocyte colony stimulating factor by various kinds of stromal cells in vitro detected by enzyme immunoassay and in situ hybridization | journal = Stem Cells | volume = 12 | issue = 4 | pages = 416–23 | date = July 1994 | pmid = 7524894 | doi = 10.1002/stem.5530120409 }} * {{cite journal | vauthors = Watari K, Ozawa K, Tajika K, Tojo A, Tani K, Kamachi S, Harigaya K, Takahashi T, Sekiguchi S, Nagata S | title = Production of human granulocyte colony stimulating factor by various kinds of stromal cells in vitro detected by enzyme immunoassay and in situ hybridization | journal = Stem Cells | volume = 12 | issue = 4 | pages = 416–423 | date = July 1994 | pmid = 7524894 | doi = 10.1002/stem.5530120409 | s2cid = 22671177 }}
* {{cite journal | vauthors = Hill CP, Osslund TD, Eisenberg D | title = The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 11 | pages = 5167–71 | date = June 1993 | pmid = 7685117 | pmc = 46676 | doi = 10.1073/pnas.90.11.5167 | bibcode = 1993PNAS...90.5167H }} * {{cite journal | vauthors = Hill CP, Osslund TD, Eisenberg D | title = The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 11 | pages = 5167–5171 | date = June 1993 | pmid = 7685117 | pmc = 46676 | doi = 10.1073/pnas.90.11.5167 | doi-access = free | bibcode = 1993PNAS...90.5167H }}
* {{cite journal | vauthors = Haniu M, Horan T, Arakawa T, Le J, Katta V, Rohde MF | title = Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region | journal = Archives of Biochemistry and Biophysics | volume = 324 | issue = 2 | pages = 344–56 | date = December 1995 | pmid = 8554326 | doi = 10.1006/abbi.1995.0047 }} * {{cite journal | vauthors = Haniu M, Horan T, Arakawa T, Le J, Katta V, Rohde MF | title = Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region | journal = Archives of Biochemistry and Biophysics | volume = 324 | issue = 2 | pages = 344–356 | date = December 1995 | pmid = 8554326 | doi = 10.1006/abbi.1995.0047 }}
* {{cite journal | vauthors = McCracken S, Layton JE, Shorter SC, Starkey PM, Barlow DH, Mardon HJ | title = Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta | journal = The Journal of Endocrinology | volume = 149 | issue = 2 | pages = 249–58 | date = May 1996 | pmid = 8708536 | doi = 10.1677/joe.0.1490249 }} * {{cite journal | vauthors = McCracken S, Layton JE, Shorter SC, Starkey PM, Barlow DH, Mardon HJ | title = Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta | journal = The Journal of Endocrinology | volume = 149 | issue = 2 | pages = 249–258 | date = May 1996 | pmid = 8708536 | doi = 10.1677/joe.0.1490249 }}
{{refend}} {{refend}}


Latest revision as of 03:12, 29 September 2024

Mammalian protein found in humans

Not to be confused with granulocyte-macrophage colony-stimulating factor.
CSF3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2D9Q, 1CD9, 1GNC, 1PGR, 1RHG

Identifiers
AliasesCSF3, C17orf33, CSF3OS, GCSF, colony stimulating factor 3
External IDsOMIM: 138970; MGI: 1339751; HomoloGene: 7677; GeneCards: CSF3; OMA:CSF3 - orthologs
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)
Chromosome 17 (human)Genomic location for CSF3Genomic location for CSF3
Band17q21.1Start40,015,361 bp
End40,017,813 bp
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)
Chromosome 11 (mouse)Genomic location for CSF3Genomic location for CSF3
Band11 D|11 62.45 cMStart98,592,089 bp
End98,594,455 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • testicle

  • olfactory zone of nasal mucosa

  • vena cava

  • muscle of thigh

  • gastrocnemius muscle

  • left uterine tube

  • cartilage tissue

  • upper lobe of left lung

  • mucosa of paranasal sinus

  • gonad
Top expressed in
  • entorhinal cortex

  • embryo

  • CA3 field

  • lactiferous gland

  • cervix

  • endothelial cell of lymphatic vessel

  • Medulla Oblongata

  • primary motor cortex

  • blastocyst

  • integument
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

1440

12985

Ensembl

ENSG00000108342

ENSMUSG00000038067

UniProt

P09919

P09920

RefSeq (mRNA)

NM_000759
NM_001178147
NM_172219
NM_172220

NM_009971

RefSeq (protein)

NP_000750
NP_001171618
NP_757373
NP_757374

NP_034101

Location (UCSC)Chr 17: 40.02 – 40.02 MbChr 11: 98.59 – 98.59 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

Functionally, it is a cytokine and hormone, a type of colony-stimulating factor, and is produced by a number of different tissues. The pharmaceutical analogs of naturally occurring G-CSF are called filgrastim and lenograstim.

G-CSF also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.

Biological function

G-CSF is produced by endothelium, macrophages, and a number of other immune cells. The natural human glycoprotein exists in two forms, a 174- and 177-amino-acid-long protein of molecular weight 19,600 grams per mole. The more-abundant and more-active 174-amino acid form has been used in the development of pharmaceutical products by recombinant DNA (rDNA) technology.

White blood cells
The G-CSF-receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates proliferation and differentiation into mature granulocytes. G-CSF stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils. G-CSF regulates them using Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and Ras/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal transduction pathway.
Hematopoietic System
G-CSF is also a potent inducer of hematopoietic 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.
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 induce neurogenesis, to increase the neuroplasticity and to counteract apoptosis. These properties are currently under investigations for the development of treatments of neurological diseases such as cerebral ischemia.

Genetics

The gene for G-CSF is located on chromosome 17, locus q11.2-q12. Nagata et al. found that the GCSF gene has four introns, and that two different polypeptides are synthesized from the same gene by differential splicing of mRNA.

The two polypeptides differ by the presence or absence of three amino acids. Expression studies indicate that both have authentic GCSF activity.

It is thought that stability of the G-CSF mRNA is regulated by an RNA element called the G-CSF factor stem-loop destabilising element.

Medical use

Chemotherapy-induced neutropenia

Chemotherapy can cause myelosuppression and unacceptably low levels of white blood cells (leukopenia), making patients susceptible to infections and sepsis. G-CSF stimulates the production of granulocytes, a type of white blood cell. In oncology and hematology, a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery and reduce mortality from neutropenia after chemotherapy, allowing higher-intensity treatment regimens. It is administered to oncology patients via subcutaneous or intravenous routes. 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.

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.

A study in mice has shown that G-CSF may decrease bone mineral density.

G-CSF administration has been shown to attenuate the telomere loss associated with chemotherapy.

Use in drug-induced neutropenia

Neutropenia can be a severe side effect of clozapine, an antipsychotic medication in the treatment of schizophrenia. G-CSF can restore neutrophil count. Following a return to baseline after stopping the drug, it may sometimes be safely rechallenged with the added use of G-CSF.

Before blood donation

G-CSF is also used to increase the number of hematopoietic stem cells in the blood of the donor before collection by leukapheresis for use in hematopoietic stem cell transplantation. For this purpose, G-CSF appears to be safe in pregnancy during implantation as well as during the second and third trimesters. Breastfeeding should be withheld for three days after CSF administration to allow for clearance of it from the milk. People who have been administered colony-stimulating factors do not have a higher risk of leukemia than people who have not.

Stem cell transplants

G-CSF may also be given to the receiver in hematopoietic stem cell transplantation, to compensate for conditioning regimens.

Side effect

The skin disease Sweet's syndrome is a known side effect of using this drug.

History

Mouse granulocyte-colony stimulating factor (G-CSF) was first recognised and purified in Walter and Eliza Hall Institute, Australia in 1983, and the human form was cloned by groups from Japan and Germany/United States in 1986.

The FDA approved the first biosimilar of Neulasta in June 2018. It is made by Mylan and sold as Fulphila.

Pharmaceutical variants

The recombinant human G-CSF (rhG-CSF) synthesised in an E. coli expression system is called filgrastim. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim.

Filgrastim was first marketed by Amgen with the brand name Neupogen. Several bio-generic versions are now also available in markets such as Europe and Australia. Filgrastim (Neupogen) and PEG-filgrastim (Neulasta) are two commercially available forms of rhG-CSF. The PEG (polyethylene glycol) form has a much longer half-life, reducing the necessity of daily injections.

Another form of rhG-CSF called lenograstim is synthesised in Chinese 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

G-CSF when given early after exposure to radiation may improve white blood cell counts, and is stockpiled for use in radiation incidents.

Mesoblast planned in 2004 to use G-CSF to treat heart degeneration by injecting it into the blood-stream, plus SDF (stromal cell-derived factor) directly to the heart.

G-CSF has been shown to reduce inflammation, reduce amyloid beta burden, and reverse cognitive impairment in a mouse model of Alzheimer's disease.

Due to its neuroprotective properties, G-CSF is currently under investigation for cerebral ischemia in a clinical phase IIb and several clinical pilot studies are published for other neurological disease such as amyotrophic lateral sclerosis A combination of human G-CSF and cord blood cells has been shown to reduce impairment from chronic traumatic brain injury in rats.

See also

References

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Further reading

External links

PDB gallery
  • 1cd9: 2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR 1cd9: 2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR
  • 1gnc: STRUCTURE AND DYNAMICS OF THE HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR DETERMINED BY NMR SPECTROSCOPY. LOOP MOBILITY IN A FOUR-HELIX-BUNDLE PROTEIN 1gnc: STRUCTURE AND DYNAMICS OF THE HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR DETERMINED BY NMR SPECTROSCOPY. LOOP MOBILITY IN A FOUR-HELIX-BUNDLE PROTEIN
  • 1pgr: 2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR 1pgr: 2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR
  • 1rhg: THE STRUCTURE OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND ITS RELATIONSHIP TO THOSE OF OTHER GROWTH FACTORS 1rhg: THE STRUCTURE OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND ITS RELATIONSHIP TO THOSE OF OTHER GROWTH FACTORS
  • 2d9q: Crystal Structure of the Human GCSF-Receptor Signaling Complex 2d9q: Crystal Structure of the Human GCSF-Receptor Signaling Complex
Colony-stimulating factors
CFU-GEMM
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Granulocyte macrophage colony-stimulating factor
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