Erythroid progenitor cells

Mechanism of Action A glycoprotein that stimulates division and differentiation of erythroid progenitor cells in bone marrow. Therapeutic Effect Induces erythropoiesis and releases reticulocytes from bone marrow. 

Clinical pharmacology Erythropoietin is instrumental in the production of red cells from the erythroid tissues in the bone marrow. The majority of this hormone is produced in the kidney in response to hypoxia, with an additional 10% to 15% of synthesis occurring in the hver. Erythropoietin functions as a growth factor, stimulating the mitotic activity of the erythroid progenitor cells and early precursor cells. Chronic renal failure patients often manifest the sequelae of renal dysfunction, including anemia. Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. 

Garbossa G, Gutnisky A, Nesse A. 1996. Depressed erythroid progenitor cell activity in aluminum-overloaded mice. Miner Electrolyte Metab 22 214-218. 

Dempster AM, Snyder CA. 1990. Short term benzene exposure provides a growth advantage for granulopoietic progenitor cells over erythroid progenitor cells. Arch Toxicol 64(7) 539-544. 

Dempster AM, Snyder CA. 1991. Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term, low-level benzene exposure. Arch Toxicol 65(7) 556-561. 

Neun DJ, Penn A, Snyder CA. 1994. Erythroid progenitor cells that survive benzene exposure exhibit greater resistance to the toxic benzene metabolites benzoquinone and hydroquinone. Arch Toxicol 68 535-540. 

Bryostatin 1 binds to the regulatory domain of protein kinase C short-term exposure promotes activation of protein kinase C, whereas prolonged exposure promotes significant down-regulation (4). In preclinical and phase I clinical studies it had promising antitumor and immuno-modulating effects. It amplifies expansion of myeloid and erythroid progenitor cells stimulated by the cytokines GM-CSF, M-CSF, and IL-3. Similarly, it induces the production of peripheral blood mononuclear cells with enhanced lymphokine-activated killer cell activity and proliferation in the presence of IL-2 (5). 

To illustrate this Important point, let s extend our example of a typical erythroid progenitor cell. The for binding of erythropoietin (Epo) to its receptor is about 10 M. As we noted above, only 10 percent of the 1000 cell-surface erythropoietin receptors on the surface of a cell must be bound to ligand to induce the maximal cellular response. We can determine the ligand concentration, [L], needed to Induce the maximal response by rewriting Equation 13-2 as follows ... 

Erythropoietin, a cytokine secreted by kidney cells, prevents apoptosis and promotes proliferation and differentiation of erythroid progenitor cells in the bone marrow. An excess of erythropoietin or mutations in its receptor that prevent down-regulation result in production of elevated numbers of red blood cells. 

Low concentrations of zidovudine inhibit human myeloid and erythroid progenitor cell growth (0.3 to 0.6 pg/ml) and blastogenesis in peripheral blood mononuclear cells. 

The JAK-STAT pathway of the Epo receptor is essential for proliferation and differentiation of erythroid progenitor cells. 

The marketed products are formulated as a sterile, colorless, preservative-free liquid for intravenous or subcutaneous administration. The vial should not be shaken, or the glycoprotein may become denatured, rendering it inactive. Epoetin alpha is indicated for the treatment of various anemias. Several of the conditions are listed in Table 6.4. Epoetin alpha represents a major scientific advance in the treatment of patients with chronic renal failure, serving as a replacement therapy for inadequate production of endogenous EPO by failing kidneys. Epoetin alpha may decrease the need for infusions in dialysis patients. By several mechanisms related to elevating the erythroid progenitor cell pool, epoetin alpha increases the production of red blood cells. 

Osterode, W., U. Bamas, and K. Geissler. 1999. Dose dependent reduction of erythroid progenitor cells and inappropriate erythropoietin response in e q)osure to lead New aspects of anaemia induced by lead. Occup. Environ. Med. 56(2) 106-109. Park, S.K., J. Schwartz, M. Weisskopf, D. Sparrow, P.S. Vokonas, R.O. Wright, B. Coull, H. Nie, and H. Hu. 2006. Low-level lead exposure, metabohc syndrome, and heart rate variability The VA Normative Aging Study. Environ. Health Perspect. 114(11) 1718-1724. 

Unverzagt KL, Martinson J, Lee W, Stiff PJ, Williams S, Bender JG (1996) Identification of human erythroid progenitor cell population which express the CD34 antigen and binds the plant lectin Ulex europaeus I. Cytometry 23 54-58... 

Osterode, W., Bamas, D., Geissler, K., 1999. Dose dependent reduction of erythroid progenitor cells and inappropriate erythropoietin response in exposure to lead new aspects of anaemia induced by lead. Occup. Environ. Med. 56, 106—109. 

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