Interferon-gamma enhances megakaryocyte colony-stimulating activity in murine bone marrow cells.
We have demonstrated previously that interferon-gamma (IFN-gamma) accelerates platelet recovery in mice with 5-FU induced-marrow aplasia in vivo. However, the mechanism for the regulation of megakaryocyte development induced by IFN-gamma in bone marrow cells in vivo remains unknown. To further study the effects of IFN-gamma on megakaryocyte development, various steps during IFN-gamma-mediated accelerated differentiation of the megakaryocytes were investigated in serum-free cultures of murine bone marrow cells in vitro. IFN-gamma markedly induced acetylcholine esterase (AChE) activity, a marker of murine megakaryocytic cells, accompanied by increased colony formation of the megakaryocyte lineage. A prominent increase in megakaryocyte number was observed after IFN-gamma treatment. All of these effects were dependent on the presence of IL-3, and, therefore, these results suggest that IFN-gamma acts as a megakaryocyte potentiator (Meg-POT). However, IFN-gamma did not enhance megakaryocyte maturation with respect to increase in cell size. The effects of IFN-gamma on megakaryocyte maturation were similar to those observed after treatment with higher doses of IL-3 alone. Meg-POT is defined as a factor that induces megakaryocyte maturation. Since IFN-gamma enhanced IL-3-dependent megakaryocyte colony formation and proliferation rather than megakaryocyte maturation, the effects on megakaryocyte development, which were induced by IFN-gamma treatment, seem to be different from the effects of a Meg-POT. We, therefore, propose a new function for IFN-gamma as an enhancer of megakaryocyte colony-stimulating factor activity. The effect of IFN-gamma in vitro appears to correlate well with the acceleration of platelet recovery in vivo.
Tsuji-Takayama
K
K
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Tahata
H
H
Harashima
A
A
Nishida
Y
Y
Izumi
N
N
Fukuda
S
S
Ohta
T
T
Kurimoto
M
M
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D004357:Drug Synergism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D007371:Interferon-gamma; D000110:Acetylcholinesterase