Erythropoietin: structure, control of production, and function

W Jelkmann - Physiological reviews, 1992 - journals.physiology.org
Physiological reviews, 1992journals.physiology.org
Hemopoiesis counterbalances the continuous loss of aged blood cells. Young progeny are
generated by myeloid and lymphoid progenitors that originate from a small pool of
pluripotent stem cells. Blood cell counts are fairly constant in health. The rates of the
proliferation and differentiation of blood cell lineage-specific progenitors can greatly
increase in response to disorders such as hemorrhage or infection. Hemopoiesis is
controlled by several glycoprotein hormones and paracrine peptides. Apart from …
Hemopoiesis counterbalances the continuous loss of aged blood cells. Young progeny are generated by myeloid and lymphoid progenitors that originate from a small pool of pluripotent stem cells. Blood cell counts are fairly constant in health. The rates of the proliferation and differentiation of blood cell lineage-specific progenitors can greatly increase in response to disorders such as hemorrhage or infection. Hemopoiesis is controlled by several glycoprotein hormones and paracrine peptides. Apart from erythropoietin, these include thrombopoietin(415), at least three different myeloid colony-stimulating factors (GM-CSF, G-CSF, M-CSF) in the granulocytic-monocytic lineage (122, 431, 522), and the various interleukins, which not only activate the lymphocytic system but also modulate the rate of proliferation of myeloid progenitors (21, 431, 489, 522). Several of the human genes coding for hemopoietic growth factors have been isolated and cloned recently. The recombinant proteins are available for studies of their structure and function and for therapeutic purposes. Erythropoietin is an essential growth factor in the erythrocytic lineage. One percent of all red blood cells are destroyed daily and replaced by reticulocytes in healthy humans. The basal production rate of 2-3 X 1011 cells/day greatly increases when the blood O2 availability is lowered. Lack of O2 induces erythropoietin gene expression in the kidneys (38, 52,586) and the liver (38, 52). The plasma level of erythropoietin may rise l, OOO-fold above normal in severe anemia or hypoxemia. Purification of a few milligrams of the hormone from human urine was accomplished by Miyake et al.(453) in 1977. This work was a landmark in erythropoietin research. The pure urinary protein enabled investigators to carry out the first reliable radioimmunoassays for the hormone (95, 228, 597) instead of the laborious
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