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. 1982 Oct;70(4):752–761. doi: 10.1172/JCI110671

Synthesis of hemoglobin F in adult simian erythroid progenitor-derived colonies.

R M Macklis, J Javid, J M Lipton, M Kudisch, P K Pettis, D G Nathan
PMCID: PMC370283  PMID: 6181096

Abstract

The simian hematopoietic system is known to respond to anemic stress with the production of erythrocytes containing large amounts of fetal hemoglobin. To determine the regulatory mechanism responsible for hemoglobin F (HbF) production in stress erythropoiesis, adult simian bone marrow cells were cultured in plasma clots in the presence or absence of erythropoietin and burst-promoting activities, and the HbF content of progenitor-derived colonies was determined by radioimmunoligand assay. Three classes of erythroid progenitors were detected: BFU-E, CFU-E, and a very mature cohort of dense highly erythropoietin-responsive cells (HERC). These classes varied in inverse proportion to their maturity with respect to their potential for HbF accumulation in the colonies to which they give rise. Both erythropoietin and burst-promoting activity stimulated HbF production, particularly in colonies derived from immature progenitors. For example, under conditions of high erythropoietin stimulation, BFU-E colonies contained 13.7-37.7% HbF, CFU-E colonies contained 2.8-13.5% HbF, and HERC colonies 0-1% HbF. These results suggest that under nonstress conditions simian erythrocytes are derived almost entirely from HERC progenitors and proerythroblasts in which gamma chain synthesis is suppressed. During stress erythropoiesis, augmented HbF accumulation could be explained by the rapid entrance into the marrow of proerythroblasts directly derived from immature progenitors. Gamma chain production in these proerythroblasts is additionally regulated by the changes in environmental erythropoietin and burst-promoting activities.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALPEN E. L., CRANMORE D. Cellular kinetics and iron utilization in bone marrow as observed by Fe59 radioautography. Ann N Y Acad Sci. 1959 Jun 25;77:753–765. doi: 10.1111/j.1749-6632.1959.tb36938.x. [DOI] [PubMed] [Google Scholar]
  2. Alter B. P., Jackson B. T., Lipton J. M., Piasecki G. J., Jackson P. L., Kudisch M., Nathan D. G. Control of the simian fetal hemoglobin switch at the progenitor cell level. J Clin Invest. 1981 Feb;67(2):458–466. doi: 10.1172/JCI110054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clarke B. J., Nathan D. G., Alter B. P., Forget B. G., Hillman D. G., Housman D. Hemoglobin synthesis in human BFU-E and CFU-E-derived erythroid colonies. Blood. 1979 Oct;54(4):805–817. [PubMed] [Google Scholar]
  4. Darbre P. D., Lauckner S. M., Adamson J. W., Wood W. G., Weatherall D. J. Haemoglobin synthesis in human erythroid bursts during ontogeny: reproducibility and sensitivity to culture conditions. Br J Haematol. 1981 Jun;48(2):237–250. [PubMed] [Google Scholar]
  5. DeSimone J., Biel S. I., Heller P. Stimulation of fetal hemoglobin synthesis in baboons by hemolysis and hypoxia. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2937–2940. doi: 10.1073/pnas.75.6.2937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DeSimone J., Heller P., Adams J. G. Hemopoietic stress and fetal hemoglobin synthesis: comparative studies in vivo and in vitro. Blood. 1979 Nov;54(5):1176–1181. [PubMed] [Google Scholar]
  7. Dean A., Schechter A. N., Papayannopoulou T., Stamatoyannopoulos G. Heterogeneity of erythroid precursor cells. Hemoglobin quantitation in single clones by radioimmunoassay. J Biol Chem. 1981 Mar 10;256(5):2447–2453. [PubMed] [Google Scholar]
  8. Deubeleiss K. A., Dancey J. T., Harker L. A., Cheney B., Finch C. A. Marrow erythroid and neutrophil cellularity in the dog. J Clin Invest. 1975 Apr;55(4):825–832. doi: 10.1172/JCI107993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dover G. J., Boyer S. H., Charache S., Heintzelman K. Individual variation in the production and survival of F cells in sickle-cell disease. N Engl J Med. 1978 Dec 28;299(26):1428–1435. doi: 10.1056/NEJM197812282992603. [DOI] [PubMed] [Google Scholar]
  10. Dover G. J., Boyer S. H. Quantitation of hemoglobins within individual red cells: asynchronous biosynthesis of fetal and adult hemoglobin during erythroid maturation in normal subjects. Blood. 1980 Dec;56(6):1082–1091. [PubMed] [Google Scholar]
  11. Dover G. J., Ogawa M. Cellular mechanisms for increased fetal hemoglobin production in culture. Evidence for continuous commitment to fetal hemoglobin production during burst formation. J Clin Invest. 1980 Nov;66(5):1175–1178. doi: 10.1172/JCI109949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eaves C. J., Eaves A. C. Erythropoietin (Ep) dose-response curves for three classes of erythroid progenitors in normal human marrow and in patients with polycythemia vera. Blood. 1978 Dec;52(6):1196–1210. [PubMed] [Google Scholar]
  13. Golde D. W., Bersch N., Quan S. G., Lusis A. J. Production of erythroid-potentiating activity by a human T-lymphoblast cell line. Proc Natl Acad Sci U S A. 1980 Jan;77(1):593–596. doi: 10.1073/pnas.77.1.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Javid J., Pettis P. K., Miller J. E. Radio-ligand immunoassay for human hemoglobin variants. J Immunol Methods. 1981;41(2):247–255. doi: 10.1016/0022-1759(81)90247-7. [DOI] [PubMed] [Google Scholar]
  15. Kennedy W. L., Alpen E. L., Garcia J. F. Regulation of red blood cell production by erythropoietin: normal mouse marrow in vitro. Exp Hematol. 1980 Oct;8(9):1114–1122. [PubMed] [Google Scholar]
  16. Kidoguchi K., Ogawa M., Karam J. D., Martin A. G. Augmentation of fetal hemoglobin (HbF) synthesis in culture by human erythropoietic precursors in the marrow and peripheral blood: studies in sickle cell anemia and nonhemoglobinopathic adults. Blood. 1978 Dec;52(6):1115–1124. [PubMed] [Google Scholar]
  17. McLeod D. L., Shreeve M. M., Axelrad A. A. Improved plasma culture system for production of erythrocytic colonies in vitro: quantitative assay method for CFU-E. Blood. 1974 Oct;44(4):517–534. [PubMed] [Google Scholar]
  18. Monette F. C., Ouellette P. L., Faletra P. P. Characterization of murine erythroid progenitors with high erythropoietin sensitivity in vitro. Exp Hematol. 1981 Mar;9(3):249–256. [PubMed] [Google Scholar]
  19. Ouellette P. L., Monette F. C. Erythroid progenitors forming clusters in vitro demonstrate high erythropoietin sensitivity. J Cell Physiol. 1980 Oct;105(1):181–184. doi: 10.1002/jcp.1041050119. [DOI] [PubMed] [Google Scholar]
  20. Papayannopoulou T., Brice M., Stamatoyannopoulos G. Hemoglobin F synthesis in vitro: evidence for control at the level of primitive erythroid stem cells. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2923–2927. doi: 10.1073/pnas.74.7.2923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Papayannopoulou T., Kalmantis T., Stamatoyannopoulos G. Cellular regulation of hemoglobin switching: evidence for inverse relationship between fetal hemoglobin synthesis and degree of maturity of human erythroid cells. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6420–6424. doi: 10.1073/pnas.76.12.6420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Papayannopoulou T., Nakamoto B., Kurachi S., Stamatoyannopoulos G. Globin synthesis in erythroid bursts that mature sequentially in culture. I. Studies in cultures of adult peripheral blood BFU-Es. Blood. 1981 Nov;58(5):969–974. [PubMed] [Google Scholar]
  23. Roodman G. D., Kaplan J. M., Kaplan M. E., Zanjani E. D. Effects of shortened erythropoietin exposure on sheep marrow cultures. Br J Haematol. 1981 Feb;47(2):195–201. doi: 10.1111/j.1365-2141.1981.tb02779.x. [DOI] [PubMed] [Google Scholar]
  24. Salvado A. J., Sytkowski A. J. Characterization of multiple erythroid progenitors available in large quantity from rabbit marrow. Exp Hematol. 1981 Jul;9(6):595–603. [PubMed] [Google Scholar]
  25. Terasawa T., Ogawa M., Porter P. N., Golde D. W., Goldwasser E. Effect of burst-promoting activity (BPA) and erythropoietin on hemoglobin biosynthesis in culture. Blood. 1980 Dec;56(6):1106–1110. [PubMed] [Google Scholar]

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