Effects in vivo of purified recombinant human activin and erythropoietin in mice.
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/Wv and Sl/Sld 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.
Broxmeyer
H E
HE
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202-5121.
Hangoc
G
G
Zucali
J R
JR
Mason
A
A
Schwall
R
R
Carow
C
C
Cooper
S
S
D028341:Activins; D000818:Animals; D004921:Erythropoietin / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007265:Inhibins / Q000302:isolation & purification / Q000494:pharmacology*; D007501:Iron / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D012156:Reticulocytes / Q000378:metabolism
D011994:Recombinant Proteins; D028341:Activins; D004921:Erythropoietin; D007265:Inhibins; D007501:Iron