Effects in vivo of purified recombinant human activin and erythropoietin in mice

H. E. Broxmeyer, G. Hangoc, J. R. Zucali, A. Mason, R. Schwall, C. Carow, S. Cooper

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Abstract

Activin has been shown to act in vitro as an erythroid specific enhancing activity for erythropoietin (epo)-stimulated erythroid (BFU-E) and multipotential (CFU-GEMM) progenitor cells. To evaluate effects in vivo, purified recombinant activin-A and epo were administered s.c. to hypertransfused polycythemic mice for analysis of iron (59Fe) uptake, and to previously untreated mice for effects on reticulocyte release and proliferation of bone marrow (BM) and spleen (Spl) hematopoietic progenitors (CFU-GEMM, BFU-E, CFU-GM) and BM stem (CFU-S) cells. Activin alone had no effect in polycythemic BDF1 mice, but synergised with epo to significantly enhance 59Fe-incorporation into erythrocytes. In untreated C3H/HeJ mice, a single dose of activin enhanced reticulocyte release in 24 h to the level seen with epo. Activin plus epo did not further enhance reticulocyte release. Reticulocyte release was still apparent at day 4 in mice given epo twice a day for 3 days, but not in mice given activin twice a day for 3 days. Activin or epo each significantly enhanced the percent cells in S-phase of BM and Spl CFU-GEMM, BFU-E and CFU-GM in C3H/HeJ, W/W(v) and Sl/Sl(d) mice and BM CFU-S in BDF1 mice. The combination of epo plus activin did not further enhance proliferation. These results demonstrate activin's erythropoietic enhancing activities in vivo, and also activin and epo induction of enhanced proliferation of non-erythroid, as well as erythroid progenitors.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalInternational Journal of Hematology
Volume54
Issue number6
StatePublished - Dec 12 1991

ASJC Scopus subject areas

  • Hematology

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    Broxmeyer, H. E., Hangoc, G., Zucali, J. R., Mason, A., Schwall, R., Carow, C., & Cooper, S. (1991). Effects in vivo of purified recombinant human activin and erythropoietin in mice. International Journal of Hematology, 54(6), 447-454.