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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.
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.
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]
The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection.
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.
CFU-GEMM gives rise to CFU-GM (leading to monoblasts and myeloblasts), CFU-Meg (leading to megakaryoblasts), and CFU-E (leading to proerythroblasts). The stem cell will follow a specific lineage depending on the presence of certain growth factors and cytokines. The GM-CSF and IL-3 both work together to stimulate production of all lines.