Response of Early Erythroid Precursors to Bleeding

Hanna, Ismail R. A.

doi:10.1038/214355a0

Cited by 28 publications

(11 citation statements)

References 1 publication

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“…The trends shown in figure 2 seem to represent a stream of cells entering the erythroid compartment during the period of stimulation with a significantly increased rate of proliferation. A reported increase in 3H-thymidine incorporation by morphologically unidentified erythroid precursors soon after bleeding [32] supports this thesis. It appears, therefore, that the erythropoietic stimulus had a dual effect on the precursor cell: (a) it initiated its differentiation, and (b) it increased and determined its rate of proliferation.…”

Section: Resultssupporting

confidence: 73%

Identity of Erythroblast Precursors in Bone Marrow

et al. 1970

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Section: Resultssupporting

confidence: 73%

Identity of Erythroblast Precursors in Bone Marrow

et al. 1970

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“…It seems reasonable therefore to conclude that the accelerated repopulation of the ERC compartment in erythropoietin-injected Myleran mice was the result of an erythropoietinstimulated increase in their ERC proliferation. Increases in ERC proliferation in normal rats or mice during accelerated erythropoiesis have been reported on the basis of experiments employing PE precursor labeling in rats (Hanna, 1967;Blackett, 1968b), or inhibition of DNA synthesis in mice (Morse et nl., 1970). Our results supplement these findings and demonstrate a direct causal relationship between erythropoietin and increase in ERC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Erythropoietin on Proliferation of Erythropoietin‐responsive Cells

Reißmann

Udupa

1972

Cell Proliferation

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A B S T R A C TA single dose of Myleran suppressed CFU in polycythemic mice to around 1 % of normal for a period of 2 weeks and permitted the study of effects of erythropoietin on unipotential, erythroid stem cells (erythropoietin-responsive cells, ERC) in the absence of cell inflow from the CFU compartment. Without erythropoietin no ERC were detectable for 12 days after Myleran. Injections of erythropoietin had no effect on CFU but restored ERC populations in proportion to the dose of erythropoietin. Hydroxyurea given after erythropoietin markedly inhibited ERC repopulation and the latter is attributed to a stimulation of ERC proliferation by erythropoietin. Evidence in support of an age structure in the ERC population is presented. Daily erythropoietin injection resulted in stable ERC populations, indicating that ERC loss through differentiation and ERC self-replication were in balance. I N T R O D U C T I O NErythropoietin (Ep) regulates erythropoiesis by governing the rate of differentiation of erythropoietin-responsive cells (ERC) into proerythroblasts (PE), the earliest erythroblasts that can be recognized morphologically. Evidence is mounting to indicate that ERC are not identical with the pluripotential transplantable stem cells (CFU). It now appears likely that the CFU first undergo a partial differentiation into unipotential erythroid stem cells or ERC and these are then induced by erythropoietin to differentiate into PE (Lajtha et al., 1969). During accelerated erythropoiesis, a greater number of ERC is forced into differentiation, and if the ERC population is to be sustained, the greater cell outflow must be balanced either by an increased inflow from the CFU compartment or by increased self-replication of ERC. The exact mechanism and the regulation of this important step in erythropoiesis remain to be elucidated. We have presented evidence of a marked proliferative capability of ERC and have shown that erythropoietin stimulates this process (Reissmann & Samorapoompichit,

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“…As an explanation of the latter, it has been postulated that stem cells, after surviving the injury, enter replicating cycles and are thereby unresponsive to erythropoietin until a normal stem cell population has been restored (1). From autoradiographic studies in polycythemic mice or rats it appeared however that and % of the differentiating proerythroblasts were the progency of cells in cycle ( 2 ) . The complexity of stem cell kinetics is furthermore evident from the divergent results in stem cell recovery curves after irradiation as measured by grafting methods and by erythropoietin response ( 3 ) .…”

mentioning

confidence: 92%

“…If the erythropoietin-sensitive stem cell is indeed derived from a more primitive precursor, it would be entirely conceivable that erythropoietin would also enhance this process. By autoradiographic methods, Hanna ( 2 ) found bleeding to increase markedly the proliferative activity of the immediate precursors, suggesting perhaps that the high erythropoietin levels induced by bleeding exerted a direct control on the progenitor cells. The large dose of erythropoietin injected af-ter 5-FU thus might have primarily acted by restoring the immediate precursor population.…”

mentioning

confidence: 96%

Effect of Erythropoietin on Early Recovery of Erythropoiesis in Mice after Sublethal Dose of 5-Fluorouracil

Reißmann

Samorapoompichit

1968

Experimental Biology and Medicine

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The erythroid marrow population is not self-sustaining but requires influx from a precursor compartment of cells which are transformed by the action of erythropoietin into the earliest recognizable erythroblasts. The same process restores the erythroid marrow population after its eradication by radiation or by myelocytoxic drugs. Delays in erythroid repopulation after such injuries are therefore attributed to a lack of stem cell differentiation and could be the result of either an absence of erythropoietin-sensitive stem cells or of their temporary inability to respond to erythropoietin. As an explanation of the latter, it has been postulated that stem cells, after surviving the injury, enter replicating cycles and are thereby unresponsive to erythropoietin until a normal stem cell population has been restored (1). From autoradiographic studies in polycythemic mice or rats it appeared however that and % of the differentiating proerythroblasts were the progency of cells in cycle ( 2 ) . The complexity of stem cell kinetics is furthermore evident from the divergent results in stem cell recovery curves after irradiation as measured by grafting methods and by erythropoietin response ( 3 ) . Details on the events which result in a temporary unresponsiveness of erythroid precursors after marrow injury thus remain obscure, and the present study examines the effect of large doses of erythropoietin injected during the lag phase of marrow regeneration after 5-Fluorouracil ( 5-FU) administration. The drug inhibits DNA synthesis, and its killing effect depends on the proliferative state of the cells (4). I t was chosen because a single nonlethal injection completely eradicated erythroid cells in the marrow and the subsequent regeneration obeyed a sharply defined and reproducible time-course.

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Response of Early Erythroid Precursors to Bleeding

Cited by 28 publications

References 1 publication

Identity of Erythroblast Precursors in Bone Marrow

Identity of Erythroblast Precursors in Bone Marrow

Effect of Erythropoietin on Proliferation of Erythropoietin‐responsive Cells

Effect of Erythropoietin on Early Recovery of Erythropoiesis in Mice after Sublethal Dose of 5-Fluorouracil

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