Background: GM-CSF
GM-CSF was initially characterized as a factor that can support the
in vitro colony formation of granulocyte-macrophage progenitors. It is also a growth factor for erythroid, megakaryocyte, and eosinophil progenitors. GM-CSF is produced by a number of different cell types (including T cells, B cells, macrophages, mast cells, endothelial cells, fibroblasts, and adipocytes) in response to cytokine or inflammatory stimuli. On mature hematopoietic cells, GM-CSF is a survival factor for and activates the effector functions of granulocytes, monocytes/macrophages, and eosinophils. GM-CSF promotes a Th1 biased immune response, angiogenesis, allergic inflammation, and the development of autoimmunity. It shows clinical effectiveness in ameliorating chemotherapy-induced neutropenia, and GM-CSF transfected tumor cells are utilized as cancer vaccines. The 22 kDa glycosylated GM-CSF, similar to IL-3 and IL-5, is a cytokine with a core of four bundled alpha helices. Mature human GM-CSF shares 63% - 70% amino acid sequence identity with canine, feline, porcine, and rat GM-CSF and 54% with mouse GM-CSF. GM-CSF exerts its biological effects through a heterodimeric receptor complex composed of GM-CSF R alpha/CD116 and the signal transducing common beta chain (CD131) which is also a component of the high-affinity receptors for IL-3 and IL-5. In addition, GM-CSF binds a naturally occurring soluble form of GM-CSF R alpha. Human GM-CSF is active on canine and feline cells but not on murine cells.