title: Human multipotent adult progenitor cells transcriptionally regulate fucosyltransferase VII.
abstract: OBJECTIVE
  Targeted recruitment of leukocytes to sites of inflammation is a crucial event in normal host defense against pathogens, and attachment to and rolling on activated endothelial cells is a prerequisite first step for eventual leukocyte extravasation into sites of inflammation. These key events are mediated by interactions between glycosylated ligands expressed on leukocytes and selectins expressed on activated endothelium. Cell surface expression of selectin ligands on leukocytes is regulated by the rate-limiting enzyme fucosyltransferase VII (Fut7), and in its absence extravasation of leukocytes is severely inhibited. Multipotent adult progenitor cells (MAPCs) are an adherent cell population isolated from adult bone marrow. Intravenous administration of MAPCs provided functional improvement in multiple pre-clinical models of injury or disease, but the mechanisms by which these outcomes were achieved remain poorly understood.
  
  
  METHODS
  In vitro cell analysis studies including fluorescence-activated cell sorting, messenger RNA analysis, T-cell proliferation assays and endothelial cell binding assays were performed.
  
  
  RESULTS
  The in vitro cell analysis studies characterized the ability of MAPCs to secrete factors that transcriptionally attenuate expression of Fut7 in T cells, blocking the terminal fucosylation event in the biosynthesis of selectin ligands and reducing T-cell binding to endothelial cells.
  
  
  CONCLUSIONS
  This study presents the first example of a distinct regulatory mechanism involving transcriptional down-regulation of Fut7 by MAPCs that could modulate the trafficking behavior of T cells in vivo.
authors.affiliation: Center for Hematologic Malignancies, Division of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA; Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA; Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon, USA. Electronic address: ggb@ohsu.edu.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Burrows
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.affiliation: Athersys Inc., Regenerative Medicine Program, Cleveland, Ohio, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Hunady
authors.affiliation: Athersys Inc., Regenerative Medicine Program, Cleveland, Ohio, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lehman
authors.affiliation: Athersys Inc., Regenerative Medicine Program, Cleveland, Ohio, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Raber
authors.affiliation: Athersys Inc., Regenerative Medicine Program, Cleveland, Ohio, USA; National Center for Regenerative Medicine, Cleveland, Ohio, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Deans
authors.affiliation: Athersys Inc., Regenerative Medicine Program, Cleveland, Ohio, USA; National Center for Regenerative Medicine, Cleveland, Ohio, USA.
authors.forename: Wouter
authors.initials: W
authors.lastname: Van't Hof
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D064987:Cell- and Tissue-Based Therapy; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D039902:Multipotent Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C502597:FUT7 protein, human; D005647:Fucosyltransferases
keywords: fucosyltransferase VII; human multipotent adult progenitor cells; leukocyte extravasation; transcriptional regulation