Granulocyte colony-stimulating factor

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Crystal structure of human G-CSF
colony stimulating factor 3 (granulocyte)
Identifiers
Symbol	CSF3 GCSF, G-CSF
HUGO	2438
Entrez	1440
OMIM	138970
RefSeq	NM_172220
UniProt	P09919
PDB	1RHG
Other data
Locus	Chr. 17 q11.2-q12

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Not to be confused with granulocyte macrophage colony-stimulating factor.

Granulocyte Colony-Stimulating Factor (G-CSF or GCSF) is a hormone. It is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to pulse them out of the marrow into the blood. It also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.

G-CSF is also known as Colony-Stimulating Factor 3 (CSF 3).

1 Biological function
2 Genetics
3 Therapeutic use
4 Reference
5 External links

[edit] 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 180-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.

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

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.

[edit] Genetics

The gene for G-CSF is located on chromosome 17, locus q11.2-q12. Nagata et al. found that the GCSF gene has 4 introns, and that 2 different polypeptides are synthesized from the same gene by differential splicing of mRNA.^[1]

The 2 polypeptides differ by the presence or absence of 3 amino acids. Expression studies indicate that both have authentic GCSF activity.

[edit] Therapeutic use

G-CSF stimulates the production of white blood cells. In oncology and hematology, a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery from neutropenia after chemotherapy, allowing higher-intensity treatment regimens. Chemotherapy can cause myelosuppression and unacceptably low levels of white blood cells, making patients prone to infections and sepsis. However, in a Washington University School of Medicine study using mice, G-CSF is shown to lessen the density of bone tissue even while it increases the WBC count;^{[citation needed]} if this is found to occur in human cases it would necessitate increased consumption of calcium and vitamins A and D, and maybe drug therapy.

Itescu 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.^[2]

The recombinant human G-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 (Neupogen®) and PEG-filgrastim (Neulasta®) are two commercially-available forms of rhG-CSF (recombinant human G-CSF). The PEG (polyethylene glycol) form has a much longer half-life, reducing the necessity of daily injections.

Another form of recombinant human G-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.

[edit] Reference

^ Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, et al. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 1986;319:415-8. PMID 3484805.
^ Elizabeth Finkel, Stem Cells, 2005, ABC Books, ISBN 0 7333 1248 9