Alterations in erythropoiesis in TGF-beta 1-treated mice.
Chronic treatment of mice with transforming growth factor beta 1 (TGF-beta 1) resulted in a dose-dependent inhibition of erythropoiesis. Following 14 daily s.c. injections of 5 or 25 micrograms of TGF-beta 1, a significant degree of anemia was observed. In addition, erythroid progenitor cells were present in reduced numbers in the bone marrow and spleen. Pluripotent stem cells were present in normal numbers in the bone marrow of mice treated with 25 micrograms of TGF-beta 1. However, significantly elevated levels were present in the peripheral blood. Adequate levels of erythropoietin were present in TGF-beta 1-treated mice. Following suspension of treatment with TGF-beta 1, erythropoiesis was restored, and TGF-beta-treated mice were able to compensate the anemia. One week following treatment, only mice treated with 25 micrograms of TGF-beta 1 continued to show evidence of anemia. However, in contrast to 1 day following treatment, these mice had levels of reticulocytes that were significantly above control values. In addition, erythroid progenitor cells had returned to normal levels in the bone marrow and were present in elevated levels in the spleen in both groups of TGF-beta 1 treated mice. The results provide evidence that the anemia associated with sustained TGF-beta 1 treatment is the result, in part, of a reversible inhibition of the maturation of erythroid progenitor cells.
Miller
K L
KL
Department of Immunology, Celtrix Laboratories, Incorporated, Palo Alto 94303.
Carlino
J A
JA
Ogawa
Y
Y
Avis
P D
PD
Carroll
K G
KG
D000740:Anemia / Q000139:chemically induced; D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000032:analysis; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012156:Reticulocytes / Q000166:cytology; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D004921:Erythropoietin