Suppressive effects in vivo of purified recombinant human H-subunit
(acidic) ferritin on murine myelopoiesis
HE Broxmeyer, DE Williams, K Geissler, G Hangoc, S Cooper, DC Bicknell, S Levi and P Arosio
Department of Medicine, Walther Oncology Center, Indianapolis, IN 46223.
Purified recombinant human heavy-chain (acidic) ferritin (rHF) was assessed
in vivo in mice for effects on the proliferation (percentage of cells in
S-phase) and absolute numbers of granulocyte-macrophage (CFU-GM), erythroid
(BFU-E), and multipotential (CFU-GEMM) progenitor cells in the femur and
spleen and on the nucleated cells in the marrow, spleen, and blood. rHF
significantly decreased cycling rates and absolute numbers of marrow and
splenic hematopoietic progenitors and marrow and blood nucleated
cellularity. These effects were apparent in BDF1, C3H/Hej and DBA/2 mice
and were dose dependent, time related, and reversible. Suppressive effects
were noted within three hours for progenitor cell cycling, within 24 hours
for progenitor cell numbers, and within 48 hours for circulating
neutrophils. Additionally, hematopoietic progenitor cells in DBA/2 mice
infected with the polycythemia-inducing strain of the Friend virus complex
(FVC-P) were insensitive to the in vivo administration of rHF. These
studies demonstrate activity of rHF in vivo on myelopoiesis of normal but
not FVC-P-infected mice. Since rHF suppresses hematopoietic progenitor cell
proliferation from normal donors in vitro and from normal mice in vitro and
in vivo but does not suppress progenitor cells from patients with leukemia
in vitro or from mice with FVC-P-infection in vitro or in vivo, rHF may be
useful as a candidate adjunct molecule for the protection of normal
hematopoietic progenitor cells during chemotherapy.
Volume 73,
Issue 1,
pp. 74-79,
01/01/1989
Copyright © 1989 by The American Society of Hematology
