title: MEG-01s cells have receptors for and respond to IL-3, IL-6, and SCF.
abstract: An established megakaryoblastic cell line, MEG-01s, was used to study receptor expression and receptor-mediated responses to factors known to affect megakaryocytopoiesis. In addition, the antigenic characteristics of this cell line were further defined. MEG-01s cells were CD34+CD33+CD38 +/- HLA-DR- and expressed erythroid and granulocytic differentiation antigens as well as many megakaryocytic lineage-restricted antigens. These cells also expressed receptors for interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), as measured by flow cytometry and/or RNA expression. MEG-01s cell proliferation or survival was only marginally influenced by these factors and their combinations. c-kit, the receptor for SCF, was downmodulated by its ligand. This modulation was time-dependent, appeared to involve receptor conformational changes, and became concentration-dependent by day 3. Northern blot analysis indicated that amounts of c-kit RNA increased as downmodulation proceeded. IL-3 induced IL-6 secretion in these cells, which was augmented by a protein kinase-C (PKC) inhibitor, H7, and reduced by a tyrosine kinase inhibitor, genistein. Evidence for autocrine regulation of this cell line by IL-6 was demonstrated by the inhibitory effects of an antisense oligonucleotide on 3H-thymidine (3H-TdR) incorporation. These cells should prove useful for studies of the early signal transduction mechanisms involved in cytokine function.
authors.affiliation: Biological Products Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Kellar
authors.forename: W C
authors.initials: WC
authors.lastname: Hooper
authors.forename: J M
authors.initials: JM
authors.lastname: Benson
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D012313:RNA / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D019947:Receptors, Interleukin-6; D019089:Stem Cell Factor; D012313:RNA; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases