G-CSF is a pleiotropic cytokine best known for its specific effects on the proliferation, differentiation, and activation of hematopoietic cells of the neutrophilic granulocyte lineage. It is produced mainly by monocytes and macrophages upon activation by endotoxin, TNF-alpha and IFN-gamma. Other cell types including fibroblasts, endothelial cells, astrocytes and bone marrow stromal cells can also secrete G-CSF after LPS, IL-1 or TNF-alpha activation. In addition, various carcinoma cell lines and myeloblastic leukemia cells can express G-CSF constitutively.
The murine G-CSF cDNA encodes a 208 amino acid (aa) residue precursor protein containing a 30 aa residue signal peptide that is proteolytically cleaved to generate the 178 aa residue mature protein. Human G-CSF is 73% identical at the amino acid level to murine G-CSF and the two proteins show species cross-reactivity.
In vitro, G-CSF stimulates growth, differentiation and functions of cells from the neutrophil lineage. It also has blast cell growth factor activity and can synergize with IL-3 to shorten the Go period of early hematopoietic progenitors. Consistent with its in vitro functions, G-CSF has been found to play important roles in defense against infection, in inflammation and repair, and in the maintenance of steady state hematopoiesis. Recombinant human G-CSF has been approved for the amelioration of chemotherapy induced neutropenia as well as for severe chronic neutropenia following marrow transplant.
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