What causes blood in CSF



The Granulocyte Colony Stimulating Factor (engl. Granulocyte Colony Stimulating Factor, G-CSF) is a cell hormone that is released from the body in the event of inflammation and stimulates the formation of white blood cells. In the 1980s, the physician Karl Welte was the first researcher in the world to characterize the cell hormone and to prove its biological effects. According to the current state of research, the administration of G-CSF has the effect that 1. infectious side effects of chemotherapy can be reduced (cancer treatment) 2. neutropenia can be treated by permanent substitution of the missing granulocytes. 3. Detach stem cells from the bone marrow and get into the peripheral blood (bone marrow transplant).

G-CSF stimulates the survival and proliferation of immature progenitor cells of the haematopoietic system (pre-CFU) and determined progenitor cells for neutrophils (CFU-GM). G-CSF is given as a medication if, due to chemotherapy in cancer, the number of certain white blood cells (neutrophil granulocytes) threatens to drop to too low levels, thereby increasing the risk of infections. In most cases, G-CSF is given prophylactically before the levels have dropped too far. In the dosage that is achieved when administered as a drug, G-CSF also shortens the development time from the progenitor cells to the mature neutrophil granulocytes from approx. 7 to 1.5 days.

Furthermore, G-CSF also acts on the mature neutrophil granulocytes. These cells also have G-CSF receptors. These cells are activated by G-CSF and chemotactically find their way to the sources of infection, where they then ingest and kill the bacteria. Glycosylation could be important for these functions of the neutrophils. The process of killing bacteria is also increased by G-CSF by increasing the superoxide production in the cells.

Another effect of G-CSF affects the haematopoietic (blood-forming) progenitor cells. Here G-CSF causes the cells to be detached from their surroundings in the bone marrow. For this reason, after the administration of G-CSF, these precursor cells are partially released from the bone marrow into the peripheral blood and can be detected here. This effect is exploited by giving G-CSF to patients who are to receive high-dose chemotherapy (or to healthy blood stem cell donors), and then the precursor cells can be collected from the peripheral blood. This collection process is called apheresis. After the high-dose chemotherapy, the patients either receive their own blood stem cells back (autologous transplantation) or the blood stem cells from a donor who matches the tissue characteristics (allogeneic transplantation). This peripheral blood stem cell transplant, made possible by the administration of G-CSF and apheresis, has largely replaced bone marrow transplantation.

structure

The human glycoprotein consists of 178 amino acids, is glycosylated on the hydroxyl group of threonine 133 and has a molecular weight of 19.6 kDa.[1][2] The sugar chain makes up about 4% of the total weight and consists of α-N-acetyl-neuraminic acid, β-galactose and N-acetyl-galactosamine. The sugar chain of G-CSF plays an essential role in the stability of the protein and in the stimulation of certain functions of the neutrophils. Another essential element of the secondary structure are two disulfide bridges. The G-CSF gene is located on chromosome 17 in the locus q11.2-q12.

Medication

Today, G-CSF is produced using genetic engineering (recombinant DNA). The drug lenograstim (Granocyte) is produced in hamster ovary cells, filgrastim (Neupogen) by E. coli.

swell

  1. UniProt P09919
  2. : Hill, C.P. et al. (1993): The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors. In: Proc. Natl. Acad. Sci. UNITED STATES. Vol. 90, pp. 5167-5171. PMID 7685117 PDF

Category: Protein