| Biochem/physiol Actions | Granulocyte-colony stimulating factor is a proliferation, differentiation, survival, and activation factor for hematopoietic cells of the restricted neutrophilic granulocyte lineage. It is produced by macrophages activated by endotoxin (LPS), by monocytes activated by TNF-α with IFNγ, by fibroblasts and endothelial cells activated by IL-1 or TNF-α, and by bone marrow stromal cells activated by IL-1 or LPS. It is suggested that during the inflammatory process endotoxins stimulate tissue macrophages to produce not only G-CSF but several other cytokines, including IL-1 and TNF-α, which in turn stimulate more G-CSF release from endothelial cells and fibroblasts. G-CSF can also synergize with IL-3 to shorten the G0 period of early hematopoietic progenitors. In addition to the namesake proliferative activity, G-CSF acts on mature neutrophils to enhance their survival and to stimulate their tumorcidal activity. Human G-CSF binds and activates a 130 kD to150 kD glycoprotein single chain receptor that has been classified as a member of the hematopoietic (cytokine) receptor family, the cytokine receptor class I, or the gp130 related cytokine receptor family (although it does not apparently bind to gp130). G-CSF receptors can be found on neutrophils, myeloid leukemia cells that respond to G-CSF, bone marrow cells of neutrophilic granulocyte lineage, and on placental trophoblasts, plus a soluble form may be expressed. Two forms of human G-CSF (177 and 174 amino acids) are synthesized from a single gene by alternative splicing, but murine G-CSF is a single expressed form of 178 amino acids. Human and murine G-CSF share 73% amino acid sequence homology and full cross-reactivity. |
