GMCSF

CYTOKINES AND GROWTH FACTORS

Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor

Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) was first characterized as a growth factor that supports the in-vitro colony formation of granulocytes-macrophages progenitor cells (1, 2). It is a pleiotropic cytokine and a member of a family of endogenous cytokines of the hematopoietic system. GM-CSF is produced as a response to immune or inflammatory stimuli by activated cells of the hematopoietic system such as T cells, B cells, macrophages, mast cells and also fibroblasts and alveolar epithelial cells. It plays an important role in regulating the proliferation, differentiation, survival and activation of hematopoietic cells such as granulocytes and monocytes , neutrophiles, basophiles and eosonophoiles, erythroid cells, megakaryocytes and T cells (3, 4).
Human and mouse GM-CSF have about 56% homology and are species specific. Human GM-CSF is not active on mouse cells and vice versa. It is active on canine and feline cells (5, 6).
GMCSF is 144 amino acids, 22kDa glycoprotein. It is composed of four bundles alpha helices. Its receptor is heterodimers with a ligand-specific alpha subunit and a betac (c) subunit that is shared with the interleukin IL-3 and IL-5 receptors. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors. Cross-linking the two receptor subunits is required for receptor activation and signaling (7, 8).
GMCSF has been shown to be involved in maturation, mobilization and antigen presentation of myeloid dentritic cells (DCs) in-vivo or ex-vivo. This function promotes Th1 immune responses, cytotoxcity, anti-angiogenesis as well as allergic inflammation, and the development of autoimmunity (9-11). Therefore GMCSF can be used in immunotherapy for the treatment of immune suppressed and immune-compromised patients as well as in veterinary medicine for the same purpose (12-14). GM-CSF is also important in regulation of embryo development and pregnancy and specifically in embryo implantation and subsequent development (15, 16).

The ED50 as determined by the dose-dependant stimulation of the proliferation of human TF-1 cells (human erythroleukemic indicator cell line) is 0.1 ng/ml, corresponding to a Specific Activity of 11, 100, 000 IU/mg.