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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.
In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development. The receptor is primarily located on neutrophils , eosinophils and monocytes / macrophages , it is also on CD34+ progenitor cells ( myeloblasts ) and precursors for erythroid and megakaryocytic lineages, but only in ...
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.
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).
Lastly, activation of CSF1R is a strong chemokinetic signal, inducing macrophage polarization and chemotaxis towards the source of CSF1R ligand. This macrophage response requires rapid morphological changes which is achieved by remodeling of the actin cytoskeleton via the Src/ Pyk2 and PI3K signaling pathways. [9]
Kupffer cells are incredibly plastic cells that have the capability to polarize specific activation states and can perform different functions in different microenvironments. M1 (classical activation) and M2 (alternative activation) designate the two extremes of macrophage polarization. M1-polarized Kupffer cells produce a large amount of pro ...