On the in vivo action of erythropoietin: a quantitative analysis

Papayannopoulou, Thalia; Finch, Clement A.

doi:10.1172/jci106911

Cited by 62 publications

(23 citation statements)

References 15 publications

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“…Erythropoietin is an obligatory factor required for the proliferation and differentiation ofmore mature erythroid progenitors (CFU-E) (2,(13)(14)(15) and stimulates the proliferation of proerythroblasts and basophilic erythroblasts (16). Whether the earliest committed erythroid progenitor (BFU-E) can respond to erythropoietin is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Miller¹,

Scaduto²,

Tillotson³

et al. 1988

J. Clin. Invest.

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Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the differentiation and proliferation of erythroid cells. To determine the cellular mechanism of action of these growth factors, we measured changes in intracellular free calcium concentration (jCaJ) in single human erythroid precursors in response to recombinant erythropoietin and GM-CSF. [CaJ in immature erythroblasts derived from cultured human cord blood erythroid progenitors was measured with fluorescence microscopy digital video imaging.When stimulated with erythropoietin, [CaJ in the majority of erythroblasts increased within 3 min, peaked at 5 min, and returned toward baseline at 10 min. The percentage of cells that responded to erythropoietin stimulation increased in a dose-dependent manner. Additional stimulation with GM-CSF in cells previously exposed to erythropoietin resulted in a second [Ca¢J increase. Immature erythroblasts treated with GM-CSF followed by erythropoietin responded similarly to each factor with a rise in [Ck]. The source of transient calcium is intracellular since erythroblasts were incubated in medium devoid of extracellular calcium. Our observations suggest that changes in [CaJ may be an intracellular signal that mediates the proliferative/differentiating effect of hematopoietic growth factors.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Miller¹,

Scaduto²,

Tillotson³

et al. 1988

J. Clin. Invest.

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show abstract

“…This estimate does not include human cells identified by imaging in the spleen and throughout the skeleton; based on previous estimates that each of the lower limbs contain approximately 7.5% of total marrow, 26 overall expansion of progenitors within the marrow only was estimated as more than 1000-fold. In a more limited series of experiments with longer term follow-up, in vivo dimerization of Mpl in neonatal NOD/SCID ␥c null mice that received transplants of F36V-MPLexpressing CD34 ϩ CD38 Ϫ Lin Ϫ CD7 Ϫ cells showed high levels of human engraftment for up to 14 weeks (mean, 63%; range, 58%-68% CD45 ϩ cells with CID vs 0.03% CD45 ϩ cells without CID).…”

Section: In Vivo Signaling Through F36v-mpl Selectively Expands Both mentioning

confidence: 99%

Expansion of multipotent and lymphoid-committed human progenitors through intracellular dimerization of Mpl

Abdel‐Azim¹,

Zhu²,

Hollis³

et al. 2008

Blood

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“…Additional sites include the placenta, endothelium, and neuronal cells [3]. However, prior studies suggest that EPO increases erythroid production and releases immature forms of erythrocytes into the peripheral circulation in response to hypoxia [1,5].…”

Section: Introductionmentioning

confidence: 99%

Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis

Dulay

Buhimschi

Zhao

et al. 2008

American Journal of Obstetrics and Gynecology

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Objective-To test the hypothesis that inflammation modulates fetal erythroblastosis and/or the release of NRBCs independent of hypoxia or fetal stress. We sought to determine if fetal inflammation is associated with an elevation in neonatal NRBC count in the setting of inflammation-associated preterm birth.Study Design-The relationships between peripheral NRBC count, histological chorioamnionitis, umbilical cord interleukin-6 (IL-6), erythropoietin (EPO), cortisol and acid-base status were analyzed in 68 preterm singletons, born to mothers who had an amniocentesis to rule out infection. Proteomic profiling of amniotic fluid identified presence of intra-amniotic inflammation according to established parameters. NRBC counts were assessed within 1-hour of birth. Early-onset neonatal sepsis (EONS) was established based on hematological and microbiological indices. IL-6, EPO and cortisol levels were measured by immunoassays. Fetal acid-base status was determined within 10 minutes of delivery. Parametric or nonparametric statistics was employed.Results-Fetuses with EONS (n=19) were delivered at earlier gestational ages (mean±SD: 27.1±2.8 weeks, P=0.001) and more often by mothers with intra-amniotic inflammation (P=0.022) and histological chorioamnionitis (P<0.001). Neonates with EONS had higher absolute NRBCs Condensation:In inflammation-associated preterm birth and in the absence of hypoxia, elevated neonatal nucleated red blood cell counts may be a direct response to inflammatory mediators. Authors' Contributions:Antonette Dulay is the principal investigator and responsible author. Antonette Dulay, Irina Buhimschi and Catalin Buhimschi designed the study, generated, interpreted the data and wrote the initial draft of the manuscript. Guomao Zhao participated with processing of biological samples, performed immunoassays, revised critically the manuscript and approved the final version. Vineet Bhandari participated with aspects of data analysis and interpretation, revised critically the manuscript and approved the final version. Guoyang Luo; Sonya Abdel-Razeq; Michael Cackovic, Victor Rosenberg, Christian Pettker Stephen Thung and Mert Ozan Bahtiyar participated with patient enrollment, acquisition of demographic and clinical data, critical revision of the manuscript and approved the final version. NIH Public AccessAuthor Manuscript Am J Obstet Gynecol. Author manuscript; available in PMC 2014 May 16. Published in final edited form as: Am J Obstet Gynecol. 2008 April ; 198(4): 426.e1-426.e9. doi:10.1016/j.ajog.2008 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript counts (P=0.011). NRBC counts were directly correlated with cord blood IL-6 levels (P<0.001) but not with EPO, cortisol or parameters of acid-base status levels regardless of EONS status. These relationships remained following correction for gestational age, diabetes, intrauterine growth restriction (IUGR) and steroid exposure.Conclusion-In the setting of inflammation-associated preterm birth and in the absence of hypoxia,...

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On the in vivo action of erythropoietin: a quantitative analysis

Cited by 62 publications

References 15 publications

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Expansion of multipotent and lymphoid-committed human progenitors through intracellular dimerization of Mpl

Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis

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