Abstract
We have examined the possibility that permanent “stress” hemopoiesis in sickle cell anemia (SS) patients leads to the modification of the behavior of circulating 14 day erythroid progenitor cells (BFU-E). In these patients we find that peripheral blood BFU-E are increased in number and have high sensitivity to erythropoietin (Epo). Maximal number of BFU-E are generated from peripheral blood of SS patients at 0.3–0.75 Epo/ml of culture compared to 1.5–2.0 U Epo/ml of culture in normals. Peripheral blood adherent cells depletion leads to the shift of Epo dose response curve, so that the Epo sensitivity of BFU-E significantly decreases. This result suggests that apparent Epo hypersensitivity reflects, in fact, an increased production of a burst promoting activity (BPA) by SS peripheral blood light density adherent (PB-LDA) cells. Experiments with conditioned medium by SS PB-LDA cells confirmed this interpretation. When peripheral blood light density non-adherent (PB-LDNA) cells of SS patients or normal individuals were plated in the presence of various concentrations of SS PB-LD cells conditioned medium and constant amounts of Epo, a dose dependent increase of the number of BFU-E was observed. When the same target cells were plated in the presence of PB-LD cells conditioned medium from normal individuals, such effect does not occur. We conclude that increased BPA production may play a role in the erythropoietic regulation during constant hemopoietic stress in sickle cell anemia and might partially explain the lower than expected Epo levels in these patients.
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References
Metealf, D. 1977. In vitro cloning of normal and leukemic cells. Recent Results in Cancer Research, New York, Springer-Verlag, 1–227.
Seiff, C.A. 1987. Heamtopoietic growth factors. J. Clin. Invest. 79: 1549–1557.
Lutton, J.D., E.A. Schmalzer, A.N. Rao, S.P. Rao, and R.D. Levere. 1980. Erythroid colony studies on sickle cell anemia in hypo-proliferative crisis. Am. J. Hematol. 8: 15–21.
Pennathus-Das, R., E. Alpen, E. Vichinsky, J. Carcia, and B. Lubin. 1984. Evidence for the presence of CFU-E with increased in vitro sensitivity to erythropoietin in sickle cell anemia. Blood 63: 1168–1171.
Ogawa, M., O.C. Grush, R.F. O’Dell, H.Hara, and M.D. MacEachern. 1977. Circulating erythropoietic precursors assessed in culture: Characterization in normal men and patients with hemoglobinopathies. Blood 50: 1081–1093.
Nathan, D.G., B.P. Alter. 1980. F-cell regulation. Ann. N.Y. Acad. Sci. 344: 219–232.
Koeffler, H.P., M.J. Cline, and D.W. Golde. 1979. Spenic irradiation in myelofibrosis: Effect on circulating myeloid progenitor cells. Br. J. Haematol. 43: 69.
Metealf, D., M.A.S. Moore. 1971. Haemopoietic cells. Frontiers of biology, North-Holland Publishing Co., 24: 107.
Chervenick, P.A. 1973. Increase in circulating stem cells in patients with myelofibrosis. Blood 41: 67.
Croizat, H., D. Amato, D.L. McLeod, D. Eskinazi, and A.A. Axelrad. 1983. Differences among myeloproliferative disorders in the behavior of their restricted progenitor cells in culture. Blood 62: 578–584.
Johnson, G.R., C.G. Begley, and R.N. Matthews. 1987. Transfusion-dependent ß-thalassemia: In vitro characterization of peripheral blood multipotential and committed progenitor cells. Exp. Hematol. 15: 394–405.
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© 1988 Plenum Press, New York
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Croizat, H., Nagel, R.L. (1988). Increased BPA Production Modulates EPO Sensitivity of Circulating BFU-E in Sickle Cell Anemia. In: Tavassoli, M., Zanjani, E.D., Ascensao, J.L., Abraham, N.G., Levine, A.S. (eds) Molecular Biology of Hemopoiesis. Advances in Experimental Medicine and Biology, vol 34. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5571-7_34
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DOI: https://doi.org/10.1007/978-1-4684-5571-7_34
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