title: Macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 induces the differentiation of CD34+ hematopoietic progenitor cells into Langerhans cells under serum-free conditions without granulocyte-macrophage colony-stimulating factor.
abstract: Macrophage colony-stimulating factor has not been considered as a factor responsible for dendritic cell or Langerhans cell development from hematopoietic progenitor cells. In this study, we examined whether macrophage colony-stimulating factor could be used instead of granulocyte-macrophage colony-stimulating factor for the in vitro development of Langerhans cells from hematopoietic progenitor cells. We replaced granulocyte-macrophage colony-stimulating factor with macrophage colony-stimulating factor from a serum-free culture containing granulocyte-macrophage colony-stimulating factor, stem cell factor, Flt3 ligand, tumor necrosis factor-alpha, and transforming growth factor-beta1. This serum-free culture medium containing macrophage colony-stimulating factor, but not granulocyte-macrophage colony-stimulating factor (macrophage colony-stimulating factor culture), could induce CD1a+ Birbeck granule+ Langerin+ E-cadherin+ factor-like XIIIa Langerhans cells. As a control, the culture of hematopoietic progenitor cells in this culture medium depleted of macrophage colony-stimulating factor or transforming growth factor-beta1 resulted in far fewer or null CD1a+ cells, respectively. Macrophage colony-stimulating factor increased the number of CD1a+ cells in a concentration-dependent fashion. These macrophage colony-stimulating factor-induced Langerhans cells were different from granulocyte-macrophage colony-stimulating factor-induced Langerhans cells in their decreased expression of CD11c and their immature phenotype. The decreased expression of CD11c, however, was recovered by culturing them with granulocyte-macrophage colony-stimulating factor, while they acquired a mature phenotype qby granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, interleukin-1alpha, or lipo-polysaccharide. Macrophage colony-stimulating factor-induced Langerhans cells could stimulate allogeneic T cells. Interestingly, we could keep the growth and immature phenotypes of macrophage colony-stimulating factor-induced Langerhans cells for at least 28 d of culture. These studies demonstrated that macrophage colony-stimulating factor in cooperation with transforming growth factor-beta1 could induce Langerhans cell development from hematopoietic progenitor cells in vitro without granulocyte-macrophage colony-stimulating factor, which suggests the possibility that macrophage colony-stimulating factor plays a part in the Langerhans cell development in vivo. In addition, the culture using macrophage colony-stimulating factor presents a novel culture system to enable a large-scale and long-term culture of immature Langerhans cells.
authors.affiliation: Department of Dermatology, Tohoku University School of Medicine, Sendai 980-8574, Japan.
authors.forename: Zia U A
authors.initials: ZU
authors.lastname: Mollah
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Manome
authors.forename: Masato
authors.initials: M
authors.lastname: Mizuashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohtani
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshino
authors.forename: Hachiro
authors.initials: H
authors.lastname: Tagami
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology; D039521:CD11c Antigen / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000166:cytology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008565:Membrane Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D039521:CD11c Antigen; D016895:Culture Media, Serum-Free; D008565:Membrane Proteins; D019089:Stem Cell Factor; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor