Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis.
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.
Broxmeyer
H E
HE
Department of Medicine, Walther Oncology Center, Indianapolis, IN 46223.
Williams
D E
DE
Geissler
K
K
Hangoc
G
G
Cooper
S
S
Bicknell
D C
DC
Levi
S
S
Arosio
P
P
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002452:Cell Count / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D005293:Ferritins / Q000494:pharmacology*; D005622:Friend murine leukemia virus; D006131:Growth Inhibitors / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000187:drug effects; D011086:Polycythemia / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology*
D006131:Growth Inhibitors; D011994:Recombinant Proteins; D005293:Ferritins