title: Interferon-gamma enhances megakaryocyte colony-stimulating activity in murine bone marrow cells.
abstract: 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.
authors.affiliation: Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuji-Takayama
authors.forename: H
authors.initials: H
authors.lastname: Tahata
authors.forename: A
authors.initials: A
authors.lastname: Harashima
authors.forename: Y
authors.initials: Y
authors.lastname: Nishida
authors.forename: N
authors.initials: N
authors.lastname: Izumi
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
mesh_terms: 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
chemical_list: D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D007371:Interferon-gamma; D000110:Acetylcholinesterase