G-CSF is a peptide hormone that stimulates the formation of granulocytes. Thus, it possesses great importance in the function of the immune system. The hormone is also given as a drug to patients with a severely weakened immune system to stimulate the formation of neutrophilic white blood cells.
What is G-CSF?
G-CSF is the abbreviation for granulocyte colony-stimulating factor. It is a peptide hormone that stimulates the formation of granulocytes from pluripotent stem cells. Granulocyte colony-stimulating factor belongs to the cytokines. In general, cytokines are proteins that are responsible for the proliferation of immune cells and thus control the immune response. There are different types of cytokines. The peptide hormone G-CSF is one of the colony-stimulating factors. Chemically, human G-CSF is a glycoprotein consisting of 174 amino acids. At position 133 is the amino acid threonine, which is glycosylated at its hydroxyl group. The non-proteinogenic portion of the molecule at the glycosylated site accounts for approximately four percent of the molecular weight. It consists of the components α-N-acetyl-neuraminic acid, N-acetyl-galactosamine, and β-galactose. Glycosylation has a stabilizing influence on the protein. At the same time, it also plays an important role in certain functions such as the activation of mature granulocytes to fight current foci of infection. Furthermore, G-CSF still contains two disulfide bridges, which determine the secondary structure of the protein. In humans, the coding gene for G-CSF is located on chromosome 17.
Function, effects, and roles
As mentioned earlier, G-CSF is an important factor of the immune system. It stimulates the immature precursor cells of the hematopoietic system (hematopoietic system or pre-CFU) to differentiate and proliferate. This means that the undifferentiated pluripotent stem cells under the influence of G-CSF differentiate into granulocytes and proliferate by cell division. Granulocytes are neutrophilic white blood cells that function as so-called scavenger cells. These become effective when the organism is infected by bacteria. Thus, any bacterial infection results in the proliferation of phagocytes from undifferentiated progenitor cells. Furthermore, G-CSF also stimulates mature granulocytes to move to sites of infection in order to kill the bacteria there. In this function, the molecule is assisted by its glycosylation-bound moiety. At the site of infection, G-CSF can thus enhance the formation of hydrogen peroxide in granulocytes, making the killing of bacteria even more effective. A third function of G-CSF is to cause the detachment of hematopoietic progenitor cells from their environment in the bone marrow. This allows some of these cells to enter the peripheral blood. With further administration of G-CSF, this process can be repeated, resulting in the accumulation of pluripotent stem cells in the blood. This process is also known as apheresis. Apheresis has proven useful for stem cell donors or for patients undergoing intensive chemotherapy. In this way, chemotherapy patients can have their own stem cell-enriched blood transplanted back into them. Stem cell donors, in turn, can make a normal blood donation instead of a bone marrow donation. G-CSF thus serves as a drug and is used in chronic neutropenia (decrease in neutrophil granulocytes), chemotherapy, or stem cell transplantation.
Formation, occurrence, properties, and optimal values
G-CSF is involved in the complex homeostatic network of the organism. Granulocyte colony-stimulating factor is a component of both the immune system and the endocrine system. Bone marrow pluripotent stem cells and mature neutrophil granulocytes possess receptors for G-CSF. When required, the proteins of G-CSF bind to the receptors and thus ensure the unfolding of their effect. Each organism produces its own G-CSF. However, when the need increases, as in the case of severe infections, chemotherapy or general immunodeficiency, the hormone may have to be injected subcutaneously. Known drugs are pegfilgrastim and lipegfilgrastim. These are produced recombinantly from certain mammalian cells such as the CHO cells (Chinese Hamster Ovary) or from Escherichia coli. The amino acid sequences are identical in both forms of production. There may be differences in glycosylation.However, newer products are glycosylated at the same position as the original G-CSF. Certain forms of processing, such as PEGylation, further increase the stability and half-life of the drugs in use without altering their efficacy. To achieve this, a chemical bond of G-CSF with polyethylene glycol is created.
Diseases and disorders
Side effects may also occur with the use of G-CSF. Bone and muscle pain are the most common. These are often joined by nausea, vomiting, loss of appetite and diarrhea. Mucosal inflammation and hair loss can also occur. The complaints are the result of the increased formation of neutrophil granulocytes, which then trigger increased immune reactions. Less frequently, infiltrates are observed in the lungs, causing cough, shortness of breath and fever, among other symptoms. This can even lead to the so-called Acute Respiratory Distress Syndrome (ARDS), which indicates an intense reaction of the lungs to external damaging factors. The spleen may enlarge to the point of splenic rupture. Another symptom is increased leukocytosis, which is the increased production of white blood cells. G-CSF must not be used in the presence of sickle cell anemia, since according to an American study, severe side effects can occur here, sometimes even leading to multiple organ failure. However, many studies also show that the symptoms are usually reversible. After discontinuation of therapy with G-CSF, the side effects also disappear. Although there is an increased formation of neutrophil leukocytes during treatment with G-CSF, studies to date have not found an increased risk of developing leukemia.
