Erythroid precursor

Many cytokines play a regulatory role in processes other that immunity and inflammation. Neurotrophic factors, such as NGF and BDNF, regulate growth, development and maintenance of various neural populations in the central and peripheral nervous system. EPO stimulates the production of red blood cells from erythroid precursors in the bone marrow. 

Note BFU-E = erythroid precursor or burst-forming unit see text for details. 

BiUco N. (1997) Culture of erythroid precursor cells of individuals exposed to ionizing radiation. Cytology and Genetics. Allerton Press, inc.New York 31, 5, 54-59. 

Examining of viability of cryopreserved cells of specific phenotype by parallel determining with vital dye and analysis with flow cytometer has demonstrated that CD 13 3 and CD34 cell candidates occurred to be more sensitive to programmed cryopreservation in comparison with more differentiated erythroid precursors (glycohporin-A -positive cells). Gly-A cells viability made 93.75 1.60%. CD 34 cell viability was 79.57 4.13%,... 

The availability of biologically active i Sj.iabelled EPO facilitated the detection and study of cell surface receptors. In addition to erythroid precursors, various other cell lines were shown to express EPO receptors, at least when cultured in vitro. Many harboured two classes of receptors a high-affinity and a low-affinity form. Most appeared to express between 1000 and 3000 receptors/cell. Radiotracer experiments illustrated that the EPO receptor is rapidly internalized after ligand binding and the EPO-receptor complex is subsequently degraded within lysosomes. 

Erythropoietin is a protein produced mainly in the cortex of the kidney. Erythropoietin binds to a receptor on the surface of erythroid precursor cells. It stimulates erythropoiesis and is primarily indicated for the treatment of anemia in patients with chronic renal failure. Other indications are the management of anemia in cancer patients and in HIV positive subjects treated with anti-HIV regimens. 

It exerts its action by binding to receptor on surface of erythroid precursor cells. There is increase in intracellular concentration of calcium and arachidonate and changes in intracellular phosphorylation. It stimulates proliferation, maturation and haemoglobin formation by committed erythroid progenitors. 

Absorption, transport, and storage of iron. Intestinal epithelial cells actively absorb inorganic iron and heme iron (H). Ferrous iron that is absorbed or released from absorbed heme iron in the intestine (1) is actively transported into the blood or complexed with apoferritin (AF) and stored as ferritin (F). In the blood, iron is transported by transferrin (Tf) to erythroid precursors in the bone marrow for synthesis of hemoglobin (Hgb) (2) or to hepatocytes for storage as ferritin (3). The transferrin-iron complexes bind to transferrin receptors (TfR) in erythroid precursors and hepatocytes and are internalized. After release of the iron, the TfR-Tf complex is recycled to the plasma membrane and Tf is released. Macrophages that phagocytize senescent erythrocytes (RBC) reclaim the iron from the RBC hemoglobin and either export it or store it as ferritin (4). Hepatocytes use several mechanisms to... 

Fig. 4. In situ hybridization technique. Part of an erythroid precursor cell infected with the human parvovirus B19 and probed for viral DNA. The BI9 nucleic acid is located within the centra electron lucent area of the nucleus (N) and also at nuclear pores (arrowheads). Ch, chromatin M, mitochondrion. A three-step detection protocol was used (see ref. 5 for details). Sheep antidigoxigenin followed by rabbit antisheep Ig and then goat antirabbit Ig conjugated to 10-nm gold. Bar is 0.5 pm.

Fig. 5. Combined in.vi hybridization and immunocytochcmistry. Part of the nucleus of an erythroid precursor ceil infected with parvovirus B19. There is colabeling of the viral DNA 10-nm gold) using in situ hybridization and the B19 capside protein (5-nm gold) by immunocytochemistty over an intranuclear crystalline array (Cr) of viral particles see ref. 7 for details). Nu, nucleus Ch, heterochromatin. Bar is 0.1 pm.

The v-erbB oncogene acts to expand a pool of highly mitotic, undifferentiated erythroid precursor cells, but these are poorly tumorigenic, because they differentiate at high rates into postmitotic, end-stage red cells. Another potential oncogene, v-erbA, blocks differentiation of erythroid precursors but creates no tumors because it is unable to provide the mitogenic impetus needed to expand the pool of stem... 

In the bloodstream, ferric iron binds tightly to circulating plasma transferrin (TF) to form diferric transferrin (FeTF). Absorption of iron into erythrocytes depends on basolateral membrane receptor-mediated endocytosis of FeTF by transferrin receptor 1 (TfR 1). FeTF binds to TfR 1 on the surface of erythroid precursors. These complexes invaginate in pits on the cell surface to form endosomes. Proton pumps within the endosomes lower pH to promote the release of iron into the cytoplasm from transferrin. Once the cycle is completed,TF and TfR 1 are recycled back to the cell surface. TF and TfR 1 play similar roles in iron absorption at the basolateral membrane of crypt enterocytes (Parkilla et al., 2001 Pietrangelo, 2002). 

Mouse (Swiss- Webster) Gd 6-15 6 hr/d 10 20 (decreased circulating erythroid precursors, elevation of granulocytic Keller and Snyder 1988... 

MIC caused dose-dependent necrosis of brain cells and muscle cells (Anderson et al, 1988) of rats in culture these findings could explain neuromuscular complaints in Bhopal victims. Exposure of mice to 1-3 ppm MIC was found to inhibit erythroid precursors, pluripotent stem cells and granulocyte-macrophage progenitor recovery from this inhibitory effect was found within 3 weeks after 1 ppm but not after 3 ppm (Hong et al, 1987). At higher concentrations of 6-15 ppm, MIC inhibited cell cycling in bone marrow, alveolar cells, and T lymphocytes (Conner et al., 1987 Shelby et al, 1987) similar data were reported by others (Tice et al, 1987 Mason et al, 1987). MIC can inhibit bone marrow cell proliferation in mice (Meshram and Rao, 1988). MIC can cause necrosis in whole-brain cell cultures (Anderson et al, 1990) and inhibit differentiation in muscle cell cultures (Anderson et al, 1988). 

D. Metcalf, G. R. Johnson, and A. W. Burgess, Direct stimulation by purified GM-CSF of the proliferation of multipotential and erythroid precursor cells. Blood 55 (1980), 138-147. 

Human erythropoietin (hEpo) is a glycoprotein of 36,000 daltons, produced by the kidney in response to hypoxia. It regulates the rate of production of mature erythrocytes by stimulating the proliferation and differentiation of erythroid precursor cells. Renal failure leads to lack of this growth factor which, in turn, leads to anemia (Hillman, 1990 Cotes and Spivak, 1991). 

Vaisman, B. Fibach, E. Konijn, A. M. Utilization of intracellular ferritin iron for hemoglobin synthesis in developing human erythroid precursors. Blood 90 831-838 1997. 

In 11 hemodialysis patients who also received recombinant human erythropoietin for anemia secondary to renal failure, deferoxamine increased the proliferation of erythroid precursor cells and had a synergistic in vivo effect on eiythropoietin (79,80). 

Aucella F, Scalzulli P, Musto P, Prencipe M, Valente GL, Vigilante M, Carotenuto M, Stallone C. Synergic effect of desferoxamine (DFO) and recombinant erythropoietin on erythroid precursors proliferation in chronic renal failure. G Ital Nefrol 1998 15 241-7. 

T-celi proliferation Basophil proliferation Erythroid precursor proliferation... 

The hormone EPO, 90% of which is produced by the kidneys, initiates and stimulates the production of RBCs. Erythropoiesis is driven by a feedback loop. The main mechanism of action of EPO is to prevent apoptosis, or programmed cell death, of erythroid precursor cells and to allow their proliferation and subsequent maturation. A decrease in tissue oxygen concentration signals the kidneys to increase the production and release of EPO into the plasma, which (1) stimulates stem cells to differentiate into proerythroblasts, (2) increases the rate of mitosis, (3) increases the release of reticulocytes from the marrow, and (4) induces Hgb formation. In normal circumstances, the RBC mass is kept at an almost constant level by EPO matching new erythrocyte production to the namral rate of loss of RBCs. Accelerated Hgb synthesis makes it possible to achieve the critical Hgb concentration necessary for RBCs to mature more rapidly, and a feedback mechanism stops further RBC nucleic acid synthesis, causing an earlier release of reticulocytes. Early appearance of large quantities of reticulocytes in the peripheral circulation (reticulocytosis) is another indication of increased RBC production. 

Molecular basis of macrocytosis Abnormal proliferation of erythroid precursors in the bone marrow, since folate deficiency encumbers the maturation of these cells by inhibition of deoxyribonucleic acid (DNA) synthesis. 

Megaloblastic anemia An anemia characterized by macrocytic erythrocytes produced by abnormal prohferation of erythroid precursors in the bone marrow due to a limitation in normal DNA synthesis. 

A severe decrease in P-globin levels leads to the precipitation of the a-chain, which in turn causes a defect in the maturation of the erythroid precursor, and erythropoiesis thus reducing red cell survival. The profound anemia in the affected individual stimulates the production of erythropoietin leading to the expansion of bone marrow and subsequent skeletal deformities. The hyperplasia of the bone marrow induces increased iron absorption leading to the deposition of iron in tissues. If the concentration of iron in the tissues becomes too high, it can lead to organ failure and death if appropriate therapeutic steps are not taken. 

Keywords Apoptosis - Cell cycle Erythroid differentiation Erythroid precursors ... 

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