Human multipotent adult progenitor cells transcriptionally regulate fucosyltransferase VII

Gregory G. Burrows, Richard T. Maziarz, Karen Hunady, Nicholas Lehman, Amy Raber, Robert J. Deans, Wouter van't Hof

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background aims: 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.

Original languageEnglish (US)
Pages (from-to)566-575
Number of pages10
JournalCytotherapy
Volume16
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Fucosyltransferase VII
  • Human multipotent adult progenitor cells
  • Leukocyte extravasation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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    Burrows, G. G., Maziarz, R. T., Hunady, K., Lehman, N., Raber, A., Deans, R. J., & van't Hof, W. (2014). Human multipotent adult progenitor cells transcriptionally regulate fucosyltransferase VII. Cytotherapy, 16(4), 566-575. https://doi.org/10.1016/j.jcyt.2013.08.004