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of or relating to the formation of red blood cells

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/17 16:34:54」(JST)

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Haematopoiesis ^[1]

Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' meaning "to make") is the process by which red blood cells (erythrocytes) are produced. It is stimulated by decreased O₂ in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin.^[2] This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells.^[2] In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow.^[2] In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the spleen and liver.^[3] After seven months, erythropoiesis occurs in the bone marrow. Increased level of physical activity can cause an increase in erythropoiesis.^[4] However, in humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen or liver. This is termed extramedullary erythropoiesis.

The bone marrow of essentially all the bones produces red blood cells until a person is around five years old. The tibia and femur cease to be important sites of hematopoiesis by about age 25; the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life.

Erythrocyte differentiation[edit]

In the process of red blood cell maturation, a cell undergoes a series of differentiations. The following stages of development all occur within the bone marrow:

A Hemocytoblast, a multipotent hematopoietic stem cell, becomes
a common myeloid progenitor or a multipotent stem cell, and then
a unipotent stem cell, then
a pronormoblast, also commonly called a oroerythroblast or a rubriblast.
This becomes a basophilic or early normoblast, also commonly called an erythroblast, then
a polychromatophilic or intermediate normoblast, then
an orthochromatic or late normoblast. At this stage the nucleus is expelled before the cell becomes
a reticulocyte.

The cell is released from the bone marrow after Stage 7, and so in newly circulating red blood cells there are about 1% reticulocytes. After one to two days, these ultimately become "erythrocytes" or mature red blood cells.

These stages correspond to specific appearances of the cell when stained with Wright's stain and examined by light microscopy, and correspond to other biochemical changes.

In the process of maturation, a basophilic pronormoblast is converted from a cell with a large nucleus and a volume of 900 fL to an enucleated disc with a volume of 95 fL. By the reticulocyte stage, the cell has extruded its nucleus, but is still capable of producing hemoglobin.

Essential for the maturation of red blood cells are Vitamin B₁₂ (cobalamin) and Vitamin B₉ (Folic acid). Lack of either causes maturation failure in the process of erythropoiesis, which manifests clinically as reticulocytopenia, an abnormally low amount of reticulocytes.

Characteristics seen in erythrocytes during erythropoiesis[edit]

As they mature, a number of erythrocyte characteristics change: The size of the cell is reduced and the cytoplasmic matrix increases in amount, and the staining reaction of the cytoplasm changes from blue to pinkish red because of the decrease in the amount of RNA and DNA. Initially, the nucleus is large in size and contains open chromatin. But as red blood cells mature the size of the nucleus decreases and finally disappears with the condensation of the chromatin material.^[5]

Regulation of erythropoiesis[edit]

A feedback loop involving erythropoietin helps regulate the process of erythropoiesis so that, in non-disease states, the production of red blood cells is equal to the destruction of red blood cells and the red blood cell number is sufficient to sustain adequate tissue oxygen levels but not so high as to cause sludging, thrombosis, or stroke. Erythropoietin is produced in the kidney and liver in response to low oxygen levels. In addition, erythropoietin is bound by circulating red blood cells; low circulating numbers lead to a relatively high level of unbound erythropoietin, which stimulates production in the bone marrow.

Recent studies have also shown that the peptide hormone hepcidin may play a role in the regulation of hemoglobin production, and thus affect erythropoiesis. The liver produces hepcidin. Hepcidin controls iron absorption in the gastrointestinal tract and iron release from reticuloendothelial tissue. Iron must be released from macrophages in the bone marrow to be incorporated into the heme group of hemoglobin in erythrocytes. There are colony forming units that the cells follow during their formation. These cells are referred to as the committed cells including the granulocyte monocyte colony forming units

Loss of function of the erythropoietin receptor or JAK2 in mice cells causes failure in erythropoiesis, so production of red blood cells in embryos and growth is disrupted. If there is no feedback inhibition, such as suppressors of cytokine signaling proteins in the system, that would cause giantism in mice.^[6]^[7]

References[edit]

^ Le, Tao; Bhushan, Vikas; Vasan, Neil (2010). First Aid for the USMLE Step 1: 2010 20th Anniversary Edition. USA: The McGraw-Hill Companies, Inc. p. 123. ISBN 978-0-07-163340-6.
^ ^a ^b ^c Sherwood, L, Klansman, H, Yancey, P: Animal Physiology, Brooks/Cole, Cengage Learning, 2005.
^ Palis J, Segel GB (June 1998). "Developmental biology of erythropoiesis". Blood Rev. 12 (2): 106–14. doi:10.1016/S0268-960X(98)90022-4. PMID 9661799.
^ Le, Tao; Bhushan, Vikas; Vasan, Neil (2010). First Aid for the USMLE Step 1: 2010 20th Anniversary Edition. USA: The McGraw-Hill Companies, Inc. p. 124. ISBN 978-0-07-163340-6.
^ Textbook of Physiology by Dr. A. K. Jain reprint 2006-2007 3rd edition.
^ Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S (April 2002). "Severe iron deficiency anemia in transgenic mice expressing liver hepcidin". Proc. Natl. Acad. Sci. U.S.A. 99 (7): 4596–601. doi:10.1073/pnas.072632499. PMC 123693. PMID 11930010.
^ Michael Föller, Stephan M. Huber , Florian Lang (August 2008). "Erythrocyte programmed cell death.". IUBMB Life 60 (10): 661–668. doi:10.1002/iub.106. PMID 18720418.

External links[edit]

Microscopic Hematology^{[dead link]}
More information on erythropoiesis^{[dead link]}

UpToDate Contents

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1. 透析前および腹膜透析患者における慢性腎疾患の貧血のためのエリスロポエチン erythropoietin for the anemia of chronic kidney disease among predialysis and peritoneal dialysis patients
2. 骨髄性プロトポルフィリン症 erythropoietic protoporphyria
3. 慢性腎疾患における貧血：エリスロポエチン製剤を投与した患者でのヘモグロビン／
ヘマトクリットの目標値 anemia of chronic kidney disease target hemoglobin hematocrit for patients treated with erythropoietic agents
4. 表皮水疱症の診断 diagnosis of epidermolysis bullosa
5. 先天性骨髄性ポルフィリン症 congenital erythropoietic porphyria

English Journal

Provision of Antioxidant Therapy in Hemodialysis (PATH): A Randomized Clinical Trial.

Himmelfarb J1, Ikizler TA, Ellis C, Wu P, Shintani A, Dalal S, Kaplan M, Chonchol M, Hakim RM.Author information 1Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington;AbstractIncreased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus α-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.
Journal of the American Society of Nephrology : JASN.J Am Soc Nephrol.2014 Mar;25(3):623-33. doi: 10.1681/ASN.2013050545. Epub 2013 Dec 26.
Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examin
PMID 24371300

Modeling analysis of the dynamics of thrombocytopoietic, granulocytopoietic and erythropoietic systems in irradiated humans.

Smirnova OA.Author information Federal State Unitary Enterprise Research and Technical Center of Radiation-Chemical Safety and Hygiene, 40 Shchukinskaya St, Moscow 123182, Russian Federation.AbstractBiologically motivated mathematical models, which describe the dynamics of the thrombocytopoietic, granulocytopoietic and erythropoietic systems in irradiated humans, are developed and thoroughly investigated [ 1- 3]. These models are implemented as the systems of non-linear ordinary differential equations, whose variables and constant parameters have clear biological meaning. The modeling studies revealed general regularities and characteristic features of the dynamics of the aforementioned hematopoietic lineages in acutely and chronically irradiated humans. It is shown that the modeling predictions qualitatively and quantitatively agree with the respective clinical data for humans exposed to acute and chronic irradiation in wide ranges of doses and dose rates. The 'lethal' dose rate of chronic irradiation, which is evaluated in the framework of the granulocytopoiesis model, coincides with the real minimal dose rate of lethal chronic irradiation for humans. As for the thrombocytopoiesis and erythropoiesis models, the respective 'lethal' dose rates of chronic irradiation are very close to the real one for humans. All this bears witness to the validity of employment of the developed models in the investigation and prediction of radiation effects on human hematopoiesis. These models could provide a better understanding of the risks to health from the space radiation environment for astronauts on long-term space missions. The models could also be helpful in estimating the hazards for health of a population, which resides in contaminated areas after an accident.
Journal of radiation research.J Radiat Res.2014 Mar 1;55 Suppl 1:i36. doi: 10.1093/jrr/rrt150.
Biologically motivated mathematical models, which describe the dynamics of the thrombocytopoietic, granulocytopoietic and erythropoietic systems in irradiated humans, are developed and thoroughly investigated [ 1- 3]. These models are implemented as the systems of non-linear ordinary differential eq
PMID 24585983

Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation.

Yamamoto M1, Arimura H, Fukushige T, Minami K, Nishizawa Y, Tanimoto A, Kanekura T, Nakagawa M, Akiyama S, Furukawa T.Author information 1Department of Molecular Oncology, Graduate School Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.AbstractAbcb10, member 10 of the ABC transporter family, is reportedly a part of a complex in the mitochondrial inner membrane with mitoferrin-1 (Slc25a37) and ferrochelatase (Fech) and is responsible for heme biosynthesis in utero. However, it is unclear whether loss of Abcb10 causes pathological changes in adult mice. Here, we show that Abcb10(-/-) mice lack heme biosynthesis and erythropoiesis abilities and die in midgestation. Moreover, we generated Abcb10(F/-); Mx1-Cre mice, with Abcb10 in hematopoietic cells deleted, which showed accumulation of protoporphyrin IX and maturation arrest in reticulocytes. Electron microscopy images of Abcb10(-/-) hematopoietic cells showed a marked increase of iron deposits at the mitochondria. These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia.
Molecular and cellular biology.Mol Cell Biol.2014 Mar;34(6):1077-84. doi: 10.1128/MCB.00865-13. Epub 2014 Jan 13.
Abcb10, member 10 of the ABC transporter family, is reportedly a part of a complex in the mitochondrial inner membrane with mitoferrin-1 (Slc25a37) and ferrochelatase (Fech) and is responsible for heme biosynthesis in utero. However, it is unclear whether loss of Abcb10 causes pathological changes i
PMID 24421385

Japanese Journal

A high concentration of triiodothyronine attenuates the stimulatory effect on hemin-induced erythroid differentiation of human erythroleukemia K562 cells

, , , , , ,
Endocrine Journal 62(5), 431-440, 2015
… Although thyroid hormone is a known stimulator of erythropoietic differentiation, severe anemia is sometimes observed in patients with hyperthyroidism and this mechanism is not fully understood. …
NAID 130005071801

Comparison between Long- and Short-Acting Erythropoiesis-Stimulating Agents in the Period Required for Haemoglobin Stabilisation in Treatment of Anaemia in Patients with Chronic Kidney Disease

, , , , , , , , , , , ,
Biological and Pharmaceutical Bulletin 38(5), 740-745, 2015
… Comparative studies of the potency of long- and short-acting erythropoiesis-stimulating agents (L-ESAs and S-ESAs) on erythropoietic activity in patients with chronic kidney disease without dialysis have not been performed, although L-ESAs are used in many countries. …
NAID 130005068083

ヘム合成のバイオロジーの最前線

藤原亨,張替秀郎
臨床血液 56(2), 119-127, 2015
ヘムは全ての細胞で必須の分子であるが，その主な産生細胞は赤芽球と肝細胞である。ヘム生合成の障害があると，組織への酸素輸送，ミトコンドリアでの酸化的リン酸化，薬物代謝等に重大な障害を生じ，その結果，ポルフィリン症と総称される一群の疾患を生じる。本疾患は，肝細胞におけるヘム生合成の障害を認める肝性ポルフィリン症と，赤芽球でヘム合成の障害を生じる造血性ポルフィリン症に大別される。一方，赤芽球におけるヘム …
NAID 130004920717

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リンク元	「赤血球形成」
拡張検索	「erythropoietic progenitor cell」「erythropoietic stem cell」「congenital dyserythropoietic anemia」「dyserythropoietic」