Granulocyte colony-stimulating factor

Source: Wikipedia, the free encyclopedia.
Not to be confused with granulocyte-macrophage colony-stimulating factor.
CSF3
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
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[3][4]
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

bloodstream.[5][6]

Functionally, it is a

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.[citation needed]

White blood cells
The
phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal transduction pathway.[citation needed
]
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.[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 induce
cerebral ischemia.[citation needed
]

Genetics

The gene for G-CSF is located on

polypeptides are 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 the G-CSF factor stem-loop destabilising element.[citation needed]

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.[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 decrease

bone mineral density.[15]

G-CSF administration has been shown to attenuate the telomere loss associated with chemotherapy.[16]

Use in drug-induced neutropenia

rechallenged with the added use of G-CSF.[17][18]

Before blood donation

G-CSF is also used to increase the number of

clearance of it from the milk.[19] People who have been administered colony-stimulating factors do not have a higher risk of leukemia than people who have not.[19]

Stem cell transplants

G-CSF may also be given to the receiver in

conditioning regimens.[16]

Side effect

The skin disease

Sweet's syndrome is a known side effect of using this drug.[20]

History

Mouse granulocyte-colony stimulating factor (G-CSF) was first recognised and purified in

Walter and Eliza Hall Institute, Australia in 1983,[21] and the human form was cloned by groups from Japan and Germany/United States in 1986.[10][22]

The FDA approved the first biosimilar of Neulasta in June 2018. It is made by Mylan and sold as Fulphila.[23]

Pharmaceutical variants

The

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.[citation needed
]

Filgrastim was first marketed by

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.[24][25]

SDF (stromal cell-derived factor) directly to the heart.[26]

G-CSF has been shown to reduce inflammation, reduce amyloid beta burden, and reverse cognitive impairment in a mouse model of Alzheimer's disease.[27]

Due to its neuroprotective properties, G-CSF is currently under investigation for

amyotrophic lateral sclerosis[29] A combination of human G-CSF and cord blood cells has been shown to reduce impairment from chronic traumatic brain injury in rats.[30]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108342 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038067 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 20774089
    .
  6. PMID 27943116
    .
  7. S2CID 5774130
    .
  8. PMID 16007267
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  9. PMID 18835867
    .
  10. ^
    S2CID 4325026
    .
  11. PMID 23788754
    .
  12. ^ "Granulocyte colony stimulating factor (G-CSF)". Cancer Research UK. Retrieved 12 November 2014.
  13. PMID 26343861
    .
  14. S2CID 21255495
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  15. PMID 17192391
    .
  16. ^
    S2CID 5785335
    .
  17. PMID 28747065
    .
  18. S2CID 41269943
    .
  19. ^
    PMID 23287427
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  20. S2CID 414133
    .
  21. S2CID 45170361
    .
  22. PMID 2420009
    .
  23. ^ Commissioner Oo (2019-09-11). "Press Announcements - FDA approves first biosimilar to Neulasta to help reduce the risk of infection during cancer treatment". www.fda.gov.
  24. PMID 16737941
    .
  25. PMID 18287516
    .
  26. ISBN 978-0-7333-1248-9
    .
  27. PMID 19500657
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  28. ^ "AXIS 2: AX200 for the Treatment of Ischemic Stroke - Full Text View - ClinicalTrials.gov". clinicaltrials.gov.
  29. S2CID 43087598
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  30. PMID 24621603
    .

Further reading

External links
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