title: Flt3-ligand production by human bone marrow stromal cells.
abstract: Bone marrow stromal cells are important sources of cytokines and growth factors which participate in regulation of proliferation and differentiation of hematopoietic stem and progenitor cells. Recently flt3/flk-2-ligand (flt3-L), a new growth factor which uses a membrane tyrosine kinase receptor, was cloned. It is expressed in transmembrane and soluble forms and stimulates/co-stimulates proliferation and colony formation of hematopoietic stem/progenitor cells. It has not been reported whether flt3-L is produced by cells of the hematopoietic bone marrow microenvironment. We demonstrate the expression of flt3-L in bone marrow fibroblasts (BMF) and in stromal cells of adherent layers of long-term bone marrow cultures by RT-PCR, Northern blot, immunocytochemistry and FACS analysis. The latter two methods localized flt3-L intracellularly and on cell membranes. Treatment with interleukin-1 alpha increased the expression of flt3-L in BMF. This demonstrates production and modulation of flt3-L in stromal cells of human bone marrow.
authors.affiliation: Department of Medicine (Hematology/Oncology, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lisovsky
authors.forename: S E
authors.initials: SE
authors.lastname: Braun
authors.forename: Y
authors.initials: Y
authors.lastname: Ge
authors.forename: H
authors.initials: H
authors.lastname: Takahira
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: V G
authors.initials: VG
authors.lastname: Savchenko
authors.forename: S D
authors.initials: SD
authors.lastname: Lyman
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006410:Hematopoiesis; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; C084881:flt3 ligand protein