scholarly journals Relationships between thrombopoiesis and erythropoiesis: with studies of the effects of preparations of thrombopoietin and erythropoietin

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 547-558 ◽  
Author(s):  
BL Evatt ◽  
JL Spivak ◽  
J Levin
Keyword(s):  
Ammonium Sulfate ◽  
Red Cells ◽  
Red Cell ◽  
Erythropoietic Activity ◽  
Rabbit Plasma ◽  
Ammonium Sulfate Precipitation ◽  
Sequential Fractionation ◽  
Platelet Production ◽  
Cell Production

Abstract The effects of administration of partially purified human urinary erythropoietin and rabbit thrombopoietin, and of endogenously produced erythropoietin and thrombopoietin on both red cell and platelet production were examined in mice. Partially purified thrombopoietin was prepared from rabbit plasma by sequential fractionation with ammonium sulfate precipitation, and DEAE and Sephadex G-100 chromatography. Preparations of thrombopoietin and partially purified human urinary erythropoietin (NIH No. H-11-TaLSL) were administered subcutaneously to normal mice, and the rate of incorporation of selenomethionine-75 Se into platelets was measured as an index of thrombopoietic activity of the infused material. Erythropoietin and thrombopoietin were assayed for erythropoietic activity by measuring the rate of appearance of 59Fe in the red cells of posthypoxic polycythemic mice. Preparations containing thrombopoietin had barely measurable erythropoietic activity, and 7 units of partially purified erythropoietin had little thrombopoietic activity. When endogenous levels of erythropoietin were increased by hypoxia, platelet production was not enhanced. Similarly, increased levels of thrombopoietin, induced in response to thrombocytopenia produced by platelet antiserum, did not alter red cell production. These data suggest that physiologically increased levels of thrombopoietin do not stimulate erythropoiesis, and that physiologically increased levels of erythropoietn do not stimulate thrombopoiesis. However, currently available, partially purified preparations of erythropoietin and thrombopoietin may be capable of stimulating both platelet and red cell production if used in sufficient quantities.

scholarly journals Relationships between thrombopoiesis and erythropoiesis: with studies of the effects of preparations of thrombopoietin and erythropoietin

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 547-558
Author(s):  
BL Evatt ◽  
JL Spivak ◽  
J Levin
Keyword(s):  
Ammonium Sulfate ◽  
Red Cells ◽  
Red Cell ◽  
Erythropoietic Activity ◽  
Rabbit Plasma ◽  
Ammonium Sulfate Precipitation ◽  
Sequential Fractionation ◽  
Platelet Production ◽  
Cell Production

The effects of administration of partially purified human urinary erythropoietin and rabbit thrombopoietin, and of endogenously produced erythropoietin and thrombopoietin on both red cell and platelet production were examined in mice. Partially purified thrombopoietin was prepared from rabbit plasma by sequential fractionation with ammonium sulfate precipitation, and DEAE and Sephadex G-100 chromatography. Preparations of thrombopoietin and partially purified human urinary erythropoietin (NIH No. H-11-TaLSL) were administered subcutaneously to normal mice, and the rate of incorporation of selenomethionine-75 Se into platelets was measured as an index of thrombopoietic activity of the infused material. Erythropoietin and thrombopoietin were assayed for erythropoietic activity by measuring the rate of appearance of 59Fe in the red cells of posthypoxic polycythemic mice. Preparations containing thrombopoietin had barely measurable erythropoietic activity, and 7 units of partially purified erythropoietin had little thrombopoietic activity. When endogenous levels of erythropoietin were increased by hypoxia, platelet production was not enhanced. Similarly, increased levels of thrombopoietin, induced in response to thrombocytopenia produced by platelet antiserum, did not alter red cell production. These data suggest that physiologically increased levels of thrombopoietin do not stimulate erythropoiesis, and that physiologically increased levels of erythropoietn do not stimulate thrombopoiesis. However, currently available, partially purified preparations of erythropoietin and thrombopoietin may be capable of stimulating both platelet and red cell production if used in sufficient quantities.

scholarly journals The Effect of Anemic Anoxia on the Cellular Development of Nucleated Red Cells

Blood ◽  
1959 ◽  
Vol 14 (4) ◽  
pp. 386-398 ◽  
Author(s):  
ALLAN J. ERSLEV ◽  
Elva Ruiz
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Nitrogen Mustard ◽  
Mitotic Division ◽  
Red Cells ◽  
Red Cell ◽  
Cell Production ◽  
Cellular Development

Abstract The action of an anoxic stimulus on red cell production was studied in rabbits bled 20 ml./Kg., kept anemic for 20 hours and then reinfused with the previously removed blood. This 20-hour period of anemic anoxia was followed by a characteristic reticulocyte response, a response which was modified by nitrogen mustard or colchicine administered immediately after the 20-hour period of anemia, but was not influenced by anoxia or hyperoxia in the postanemic period. When mitotic division was arrested by colchicine during the 20-hour period of anemic anoxia, the onset of the reticulocyte response, though delayed by 1 to 2 days, was otherwise of characteristic magnitude. These observations indicate that (1) the anoxic stimulus operates in the bone marrow by accelerating the differentiation of stem cells into pronormoblasts, and that thereafter (2) the maturation and multiplication of differentiated nucleated red cells proceed at fixed rates independent of the anoxic stimulus.

scholarly journals Normal Functions of the Spleen Relative to Red Blood Cells: A Review

Blood ◽  
1959 ◽  
Vol 14 (4) ◽  
pp. 399-408 ◽  
Author(s):  
WILLIAM H. CROSBY
Keyword(s):  
Cell Surface ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Normal Function ◽  
Red Cells ◽  
Red Cell ◽  
Cell Production ◽  
Normal Functions ◽  
Normal Spleen ◽  
And Storage

Abstract During all the stages of a red cell’s life the normal spleen exerts a normal function. Eight of these functions have been considered: (1) erythropoiesis; (2) an effect upon red cell production; (3) an effect upon maturation of the red cell surface; (4) the reservoir function; (5) the "culling function"; (6) iron turnover and storage; (7) the "pitting function"; (8) destruction of old red cells.

From Hematopoietic Stem Cell to Erythroblast: Regulation of Red Cell Production At Multiple Levels

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-1-SCI-1 ◽  
Author(s):  
Harvey F. Lodish
Keyword(s):  
Conflicts Of Interest ◽  
Inflammatory Diseases ◽  
Stress Hormones ◽  
Red Cells ◽  
Red Cell ◽  
Short Term ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Multiple Levels

Abstract SCI-1 Hematopoietic stem cells (HSC) undergo self-renewal and also generate all types of blood cells, including red cells, myeloid cells, and all immune system cells. Formation of red cells from HSC involves multiple cellular stages, including early erythroid-specific progenitors (burst-forming unit-erythroid [BFU-E]) that respond to several growth factors and an erythropoietin (Epo)-responsive progenitor, and the colony-forming unit-erythroid (CFU-E) that in 3 days generates ∼30 reticulocytes. In adult animals most CFU-E cells undergo apoptosis. A short-term need for red cells is met by increased Epo production by the kidney, which rescues increasing numbers of CFU-Es from apoptosis and increases red cell production over a few days. Chronic stress, such as in certain types of anemias and inflammatory diseases, leads to a marked increase in numbers of HSC and many types of progenitor cells. I will focus most of my talk on stress-triggered BFU-E proliferation and formation of CFU-Es, since our very recent work showed how glucocorticoids – an important class of stress hormones – as well as HIF-1α stimulate red cell production. Acting synergistically these allow ∼300 times more CFU-Es and erythroblasts to be formed from each BFU-E. More specifically, these molecules stimulate limited self-renewal of BFU-Es during cell division, thus maintaining progenitor immaturity and allowing over time increased numbers of CFU-E cells and thus mature red cells to be formed. This explains why certain corticosteroids are useful in treating some non-Epo responsive anemias, and I will present a molecular dissection of glucocorticoid and HIF-1α action on BFU-E progenitors that has led to the identification of genes critical for self-renewal and that suggest other possible avenues for treatment of chronic anemias. Disclosures: No relevant conflicts of interest to declare.

scholarly journals THE UTILIZATION OF IRON AND THE RAPIDITY OF HEMOGLOBIN FORMATION IN ANEMIA DUE TO BLOOD LOSS

1940 ◽  
Vol 71 (6) ◽  
pp. 731-736 ◽  
Author(s):  
P. F. Hahn ◽  
J. F. Ross ◽  
W. F. Bale ◽  
G. H. Whipple
Keyword(s):  
Blood Loss ◽  
Red Cells ◽  
Red Cell ◽  
Rapid Rate ◽  
Iron Intake ◽  
Cell Production ◽  
Feeding Experiments ◽  
Small Doses ◽  
Percentage Absorption ◽  
Almost All

The formation of hemoglobin in the anemic dog takes place at a very rapid rate. Radio-iron is detectable in the circulating red cells 4 hours after feeding. The absorbed labelled iron is entirely converted into hemoglobin within 4 to 7 days under standard anemic conditions. When red cell production has been accelerated by iron feeding or diet factors or when the dose of iron is very small, the dog can turn out as hemoglobin almost all the absorbed radio-iron in 2 to 3 days. In general, absorption of radio-iron as shown by utilization to form hemoglobin in anemic dogs is more efficient in small doses in single feeding experiments. As the iron intake is increased the percentage absorption rapidly falls.

scholarly journals Erythrokinetics: Quantitative Measurements of Red Cell Production and Destruction in Normal Subjects and Patients with Anemia

Blood ◽  
1956 ◽  
Vol 11 (4) ◽  
pp. 291-309 ◽  
Author(s):  
ELOISE R. GIBLETT ◽  
DANIEL H. COLEMAN ◽  
GIACOMO PIRZIO-BIROLI ◽  
DENNIS M. DONOHUE ◽  
ARNO G. MOTULSKY ◽  
...  
Keyword(s):  
Cell Mass ◽  
Normal Subjects ◽  
Red Cells ◽  
Red Cell ◽  
Chronic Anemia ◽  
Cell Production ◽  
Plasma Iron ◽  
Disease States ◽  
Quantitative Measurements ◽  
Normal Ratio

Abstract Red cell turnover of 19 normal subjects and 25 anemic patients was measured with the following technique: erythroid-myeloid ratio of the marrow, reticulocyte counts, plasma iron turnover, red cell utilization of radioiron, and urobilinogen determinations. Measurements of blood production and destruction were so expressed as to allow comparison between normal and anemic individuals of different size and different red cell mass. The usefulness and disadvantages of each procedure in the study of anemia are discussed. From studies of various types of anemia, it has become apparent that erythropoiesis must be defined in terms of total quantity of red cells produced and in terms of the portion of red cells produced in the marrow which are delivered to the circulating blood (effective versus ineffective erythropoiesis). A quantitative defect alone exists when a normal ratio is maintained between effective and total erythropoiesis. Here, there are changes of similar magnitude of all erythrokinetic indices, although reticulocyte and urobilinogen values are occasionally disproportionately high. The normal marrow appears to be able to increase its effective red cell production to three times normal in acute anemia and six times normal in chronic anemia. In many disease states this maximal quantitative response is impaired. Dyspoiesis of the marrow is characterized by a dissociation of erythrokinetic indices. Values which reflect total erythropoiesis (i.e., plasma iron turnover, fecal urobilinogen and erythroid-myeloid ratio of the marrow) are considerably greater than the reticulocyte level and red cell utilization of radioiron which represent effective erythropoiesis. Such defects may result in the pattern of a hemolytic process or aregenerative anemia, depending on their severity.

scholarly journals Erythrokinetics in Pernicious Anemia

Blood ◽  
1956 ◽  
Vol 11 (9) ◽  
pp. 807-820 ◽  
Author(s):  
CLEMENT A. FINCH ◽  
DANIEL H. COLEMAN ◽  
ARNO G. MOTULSKY ◽  
DENNIS M. DONOHUE ◽  
ROBERT H. REIFF
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Reticulocyte Count ◽  
Red Cells ◽  
Red Cell ◽  
Erythropoietic Activity ◽  
Ineffective Erythropoiesis ◽  
Quantitative Measurements ◽  
Marrow Activity ◽  
Made In

Abstract Quantitative measurements of the erythropoietic activity of the marrow, of circulating red cell production and destruction have been made in patients with pernicious anemia in relapse and during response to vitamin B12 therapy. Total erythropoietic marrow activity as reflected by turnover of heme components proceeds at a rate of approximately 3 times normal. The delivery of viable red cells to the circulating blood, however, does not increase above normal. This would indicate that the greater portion of marrow activity is ineffective in terms of blood production. This marrow dysfunction coupled with an increased rate of cell destruction of approximately 3 times normal is responsible for the anemia. Total erythropoiesis is somewhat less, and effective erythropoiesis considerably less, than that which may be expected of the normal marrow under the sustained stimulus of anemia. The reticulocyte count is shown to be an unreliable index of blood production in untreated pernicious anemia due to loss of reticulum from cytoplasma of many red cells before their delivery into circulation. During the response to vitamin B12 the ineffective erythropoiesis is converted to effective erythropoiesis, whereas total erythropoiesis remains unchanged. The rate of blood production during recovery is 3 to 4 times normal.

scholarly journals The Mode of Action and Nature of a Heat Stable Plasma Erythropoietic Factor

Blood ◽  
1957 ◽  
Vol 12 (12) ◽  
pp. 1101-1113 ◽  
Author(s):  
WALTER A. RAMBACH ◽  
HOWARD L. ALT ◽  
JOHN A. D. COOPER
Keyword(s):  
Bone Marrow ◽  
Cell Division ◽  
Mode Of Action ◽  
Red Cell ◽  
Erythropoietic Activity ◽  
Rabbit Plasma ◽  
Heat Stable ◽  
Stable Plasma

Abstract Boiled filtrates of "anemic" rabbit plasma have been studied by physicochemical means, and the response to their injection into the rat has been followed utilizing tracer and morphologic technics. It has been demonstrated that the erythropoietic activity of these filtrates is associated with an alpha-2 globulin, most probably a mucoprotein; and that this material produces, in the rat, an increase in the rate of red cell division and maturation, and an acceleration of release of these cells from the bone marrow and accessory organs of hemopoiesis.

scholarly journals Marrow culture in diffusion chambers in rabbits. II. Effect of competing demands for red cell and white cell production on cell growth

Blood ◽  
1978 ◽  
Vol 51 (6) ◽  
pp. 1129-1135
Author(s):  
R Willemze ◽  
RI Walker ◽  
JC Herion ◽  
JG Palmer
Keyword(s):  
Cell Growth ◽  
Peritoneal Cavity ◽  
White Cell ◽  
Red Cells ◽  
Red Cell ◽  
Diffusion Chambers ◽  
Cell Production ◽  
Competing Demands ◽  
Stimulation Of Erythropoiesis ◽  
Stimulation Of

Studies were done of cell production by marrow in diffusion chambers implanted in the peritoneal cavity of rabbits subjected to various stimuli to hematopoiesis. In chambers in neutropenic hosts and in hosts injected with endotoxin, animals presumed to have an increased stimulus to granulopoiesis, there was increased production of granulocytes but there was also increased production of red cells. Although red cell production was decreased in chambers in polycythemic hosts, granulocyte production was not different from that in controls. Stimulation of erythropoiesis by erythropoietin injections or by exposure to hypoxia increased red cell production by marrow in the implanted diffusion chambers without diminishing granulopoiesis. Only in chambers in hosts made anemic by bleeding was there an increase in red cell production accompanied by a decrease in granulocyte production. In these anemic hosts induction of neutropenia led to an increase in granulopoiesis without any depression of erythropoiesis.

scholarly journals Erythropoietic Function in Dilution Anemia

Blood ◽  
1955 ◽  
Vol 10 (6) ◽  
pp. 616-622 ◽  
Author(s):  
ALLAN J. ERSLEV
Keyword(s):  
Cardiac Output ◽  
Oxygen Content ◽  
Red Cell ◽  
Erythropoietic Activity ◽  
Cent Solution ◽  
Cell Production ◽  
Arterial Blood ◽  
Per Se ◽  
Tissue Tension

Abstract For a period of four days, four rabbits received intravenously at 12-hour intervals large amounts (25 ml./Kg.) of a 6 per cent solution of dextran. This caused a pronounced dilution anemia. However, no increase in erythropoietic activity was observed despite the reduced oxygen content of each unit of arterial blood. Since hypervolemia and dextran per se were found not to interfere with red cell production it was concluded that the increased cardiac output in dilution anemia compensates for the reduction in the oxygen content of each unit of arterial blood. Consequently, the stimulus to erythropoietic function must depend on the tissue tension of oxygen rather than on the oxygen content of arterial blood.

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