G-CSF receptors

G-CSF receptors are also found on human myeloid leukaemia cells, leu-kaemic cell lines, human placenta, trophoblastic cells, vascular endothelial 

---

The G-CSF receptor has been well characterized. It is a single transmembrane polypeptide found on the surface of neutrophils, as well as in various haemopoietic precursor cells, platelets, endothelial cells and, notably, various myeloid leukaemias. (Myeloid means derived from bone marrow leukaemia refers to a cancerous condition in which there is uncontrolled overproduction of white blood cells in the bone marrow or other blood-forming organs. The white cells produced are generally immature/abnormal and result in the suppression of production of healthy white blood cells.)... 

The extracellular region of the G-CSF receptor is heavily glycosylated (containing nine potential glycosylation sites) and displays a molecular mass in the region of 150 kDa. Two variants of the receptor in humans have been noted which display differences in the intracellular... 

G-CSF mobilizes bone marrow-derived cells into the bloodstream. These stem cells can migrate to ischemic myocardium and differentiate into cardiomyocytes, smooth muscle cells and endothelial cells. They may also induce metalloproteinases and vascular endothelial growth factor and thus play a role in tissue healing. Furthermore, G-CSF induces proliferation and enhanced survival of cardiomyocytes. This is accomplished via activation of G-CSF receptors in myocardium. G-CSF in association with TGF- 3 and collagen enhances ventricular expansion in the infarcted area. 

The neutrophil-mediated clearance was expressed as a Michaelis-Menten function, because G-CSF receptor binding is subject to saturation. The product of kcat and the ratio of ANC and ANC at baseline is the maximum velocity of drug elimination from this pathway, km is the Michaelis constant, and C is the pegfilgrastim concentration. CL2 denotes the linear clearance pathway. 

Terashi K, Oka M, Ohdo S, et al. Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients. Antimicrob. Agents Chemother. 1999 43 21-24. 

Kotto-Kome AC, FoxSE, LuW,Yang B-B, Christensen RD, Calhoun DA. Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSFusing a G-CSF-R KO model. Pharm. Res. 2004 50 55-58. 

Terashi, K., Oka, M., Ohdo, S., Furukubo, T., Ikeda, C., Fukuda, M., Soda, H., Higuchi, S., and Kohno, S., Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients, Antimicrobial Agents and Chemotherapy, Vol. 43, No. 1, 1999, pp. 21-24. 

G-CSF receptor through which pegfilgrastim and filgrastim act has been found on tumor cell lines including some myeloid, T lymphoid, lung, head and neck and bladder tumor cell lines... 

Although G-CSF is not believed to stimulate malignant lymphoid cells, G-CSF receptors have been found in patients with T cell leukemia, and this was associated with a significant increase in T cell leukemia cells in several patients (SEDA-21, 379). Other uncommon consequences of G-CSF have included blast mobilization with a phenotype change from common acute lymphoblastic leukemia to biphenotypic leukemia in one patient (87). 

IL-12R is a single-chain receptor expressed only on T cells and NK cells (structurally similar to the G-CSF receptor). 

Dong F, Hoefsloot LH, Schelen AM, et al. Identification of a nonsense mutation in the G-CSF receptor in severe congenital neutropenia. Proc Natl Acad Sci USA 1994 91 4480-4484. 

D., Andrews, R. G., Bernstein, 1. D., and Urdal, D. L. lnterleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells Receptor heterogeneity and relationship to growth factor responsiveness. Blood 74, 56-65 (1989). 

Liu F, Poursine-Laurent J, Link DC Expression of the G-CSF receptor on hematopoietic progenitor cells is not required for their mobilization by G-CSF. Blood 2000 95 3025-3031. 

Kume A, Ito K, Ueda Y et al. A G-CSF receptor-gyrase B fusion gene A new type of molecular switch for expansion of genetically modified hematopoietic cells. Biochem Biophys Res Commun 1999 260 9-12. 

---