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GM-CSF is a monomeric glycoprotein that functions as a cytokine—it is a white blood cell growth factor. [6] GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells.
Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. This ability is connected to their multiple roles in the organism: they are powerful effector cells of the innate immune system, but also important in removal of cellular debris, embryonic development and tissue repair.
The name "colony-stimulating factors" comes from the method by which they were discovered. Hematopoietic stem cells were cultured (see cell culture) on a so-called semisolid matrix, which prevents cells from moving around, so that, if a single cell starts proliferating, all of the cells derived from it will remain clustered around the spot in the matrix where the first cell was originally located.
The first signal promotes the differentiation of monocytes to macrophages and the second signal promotes immunosuppressive functions. [8] In vitro, M-CSF, IFNγ, and LPS are used for the inducement of Mregs. [7] Other cells such as eosinophils and innate lymphoid cells type 2 (ILC2) can promote M2 polarization by cytokine secretion.
Colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34) are both CSF1R ligands. Both ligands regulate myeloid cell survival, proliferation, and differentiation, but CSF-1 and IL-34 differ in their structure, distribution in the body, and the specific cellular signaling cascades triggered upon binding to CSF1R. [8]
Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. [5] [6]
In addition, after stimulation of β subunit mRNA levels coding α chain decrease and on the contrary expression of soluble α subunit is upregulated. Soluble GM-CSFRα then clutches free ligands with similar affinity as membrane receptor and prevents binding of GM-CSF to the cell surface. GM-CSFRα can be also cleaved off of the membrane receptor.
CFU-GM (Colony Forming Unit–Granulocyte–Macrophage [a]), also known as granulocyte–macrophage progenitor (GMP), is a colony forming unit. It is derived from CFU-GEMM. It is the precursor for monoblasts and myeloblasts. Production is stimulated by granulocyte macrophage colony-stimulating factor (GM-CSF).