GM-CSF was first identified in 1977 with human GM-CSF purified in 1984.
13,
14 GM-CSF is a 14- to 35-kDa glycoprotein encoded by a gene located on chromosome 5 (q23-31) close to a cluster of hematopoietic regulatory genes. GM-CSF is produced
by monocytes, macrophages, fibroblasts, endothelial cells, and conditioned lymphocytes.
6,
7 GM-CSF gene knockout mice exhibit normal hematopoiesis suggesting that it has minimal role in leukocytosis in the steady state.
6,
7 The GM-CSF receptor is expressed on neutrophils, monocytes, eosinophils, myeloid progenitors, myeloid leukemia cells, T lymphocytes, and dendritic cells. The GM-CSF receptor is composed of two subunits: an a subunit that is GM-CSF specific encoded on chromosome X/Y and a
β subunit shared by other cytokines encoded on chromosome 22q31. Binding of GMCSF to its receptor leads to downstream signaling mainly through the JAK-STAT pathway but also through mitogen-activated protein kinase (MAPK).
6,
7 GM-CSF stimulates the functional activity of
neutrophils, macrophages, monocytes, and eosinophils enhancing phagocytosis. Recombinant GM-CSF is available as sargramostim (yeast derived) and molgramostim (
Escherichia coli derived) and is approved by the US Food and Drug Administration (FDA) for use in acute myeloid leukemia (AML), autologous and allogeneic hematopoietic stem cell transplantation (SCT), and stem cell mobilization. It is used experimentally as a vaccine adjuvant.
GM-CSF augments the survival and proliferation of cells in the granulocytic and macrophage lineages as well as maintains megakaryocyte progenitors at high concentrations. Increases in granulocyte life span and metabolic functional activity have been noted in vitro. Other alterations of cellular function by GM-CSF include inhibition of neutrophil migration to sterile inflammatory fields.
15 GM-CSF is a potent stimulator (in vitro and in vivo) of dendritic cells, which are important initiators of primary immune responses.
16 Fever and fluid retention are frequently reported in patients receiving GM-CSF particularly when prepared in
E. coli.