Colony-stimulating factor
Encyclopedia
Colony-stimulating factors (CSFs) are secreted glycoprotein
s that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate
and differentiate
into a specific kind of blood cell
(usually white blood cells. For red blood cell formation, see erythropoietin
).
They may be synthesized and administered exogenously. However, such molecules can at a latter stage be detected, since they differ slightly from the endogenous ones in, e.g., features of posttranslational modification
.
Hemopoietic 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. These are referred to as "colonies." Therefore, it was possible to add various substances to cultures of hemopoietic stem cells and then examine which kinds of colonies (if any) were "stimulated" by them.
The substance that was found to stimulate formation of colonies of macrophages, for instance, was called macrophage colony-stimulating factor
, for granulocytes, granulocyte colony-stimulating factor, and so on.
- Granulocyte macrophage colony-stimulating factors (also called GM-CSF and sargramostim
) - Granulocyte colony-stimulating factor
s (also called G-CSF and filgrastim
)
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and differentiate
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
into a specific kind of blood cell
Blood cell
A blood cell, also called a hematocyte, is a cell normally found in blood. In mammals, these fall into three general categories:* red blood cells — Erythrocytes* white blood cells — Leukocytes* platelets — Thrombocytes...
(usually white blood cells. For red blood cell formation, see erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
).
They may be synthesized and administered exogenously. However, such molecules can at a latter stage be detected, since they differ slightly from the endogenous ones in, e.g., features of posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
.
Etymology
The name "colony-stimulating factors" comes from the method by which they were discovered.Hemopoietic stem cells were cultured (see cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
) 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. These are referred to as "colonies." Therefore, it was possible to add various substances to cultures of hemopoietic stem cells and then examine which kinds of colonies (if any) were "stimulated" by them.
The substance that was found to stimulate formation of colonies of macrophages, for instance, was called macrophage colony-stimulating factor
Macrophage colony-stimulating factor
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences 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. M-CSF binds to the Colony...
, for granulocytes, granulocyte colony-stimulating factor, and so on.
Mechanism
The colony-stimulating factors are soluble, in contrast to other, membrane-bound substances of the hematopoietic microenvironment. This is sometimes used as the definition of CSFs. They transduce by paracrine, endocrine, or autocrine signaling.Examples
Colony-stimulating factors include: - macrophage colony-stimulating factorMacrophage colony-stimulating factor
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences 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. M-CSF binds to the Colony...
- Granulocyte macrophage colony-stimulating factors (also called GM-CSF and sargramostim
Sargramostim
Sargramostim is a recombinant granulocyte macrophage colony-stimulating factor that functions as an immunostimulator.It is produced in yeast.-Therapeutic uses:...
) - Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 ....
s (also called G-CSF and filgrastim
Filgrastim
Filgrastim is a granulocyte colony-stimulating factor analog used to stimulate the proliferation and differentiation of granulocytes. It is produced by recombinant DNA technology. The gene for human granulocyte colony-stimulating factor is inserted into the genetic material of Escherichia coli. ...
)
- Synthetic - PromegapoietinPromegapoietinPromegapoietin is a drug given during chemotherapy to increase blood cell regeneration. It is a colony-stimulating factor that stimulates megakaryocyte production.It functions by stimulating ligands for interleukin 3 and c-Mpl....