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In critically ill patients GM-CSF has been trialled as a therapy for the immunosuppression of critical illness, and has shown promise restoring monocyte [23] and neutrophil [24] function, although the impact on patient outcomes is currently unclear and awaits larger studies. GM-CSF stimulates monocytes and macrophages to produce pro ...
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.
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.
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]
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.
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]
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).
The first signal is stimulation by M-CSF, GM-CSF, PGE2, adenosine, glucocorticoid, or apoptotic cells. [9] [18] The second signal can be stimulation with cytokines or toll-like receptor ligands. The first signal promotes the differentiation of monocytes to macrophages and the second signal promotes immunosuppressive functions. [8]