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Revision as of 13:04, 5 December 2004 by Jfdwolff (talk | contribs) (+cat)(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)Granulocyte-Colony Stimulating Factor (G-CSF) is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes. It also stimulates the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils.
G-CSF is also known as Colony-Stimulating Factor 3 (CSF 3).
G-CSF should not be confused with granulocyte macrophage colony stimulating factor (GM-CSF), which is a distinctly different haemopoietic growth factor.
Biological function
G-CSF is produced by endothelium, macrophages and a number of other immune cells. The natural human glycoprotein exists in two forms of a 174 and 180 amino acid-long protein of molecular weight 19,600 grams/mole. The more abundant and more active 174 amino acid form has been used in the development of pharmaceutical products by recombinant DNA 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 U.S.A. in 1986.
The receptor, G-CSF-receptor, is present on precursor cells in the bone marrow that, in response to stimulation by G-CSF, proliferate and differentiate into mature granulocytes.
Genetics
The gene for G-CSF is located on chromosome 17, locus q11.2-q12. Nagata et al. (1986) found that the GCSF gene has 4 introns and that 2 different polypeptides are synthesized from the same gene by differential splicing of mRNA. The 2 polypeptides differ by the presence or absence of 3 amino acids. Expression studies indicate that both have authentic GCSF activity.
Therapeutic use
G-CSF stimulates the production of white blood cells. In oncology and hematology, a recombinant form of G-CSF is used to accelerate recovery from neutropenia. Chemotherapy can cause myelosuppression and unacceptably low levels of white blood cells, making patients prone for infections and sepsis.
The recombinant human G-CSF synthesised in an E. coli expression system is called filgrastim. The structure of filgrastim differs slightly from 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. Recombinant G-CSF is also marketed under the names "Leukine" and "Sargramostim".
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.