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Evidence that specific high mannose structures directly regulate multiple cellular activities

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Abstract

Previous studies have demonstrated that much of the immunomodulatory activity of the glycoprotein uromodulin can be attributed to attached oligosaccharides. Structural studies of isolated and purified saccharides derived from uromodulin suggest that the structure Man6GlcNAc2-asn can inhibit in vitro assays of antigen driven T cell proliferation. Based on these observations, we isolated a series of high mannose glycopeptides from a variety of natural sources and tested them for biologic activity in a number of assays. We found that purified mannose rich glycopeptides are able to activate the hexose monophosphate (HMP)shunt, induce prostaglandin synthesis, and directly stimulate IL-1 synthesis. These in vitro effects appear to have in vivo counterparts. Thus in a species-restricted fashion, high mannose compounds are able to directly activate a delayed mononuclear cell infiltrate after intradermal injection. Our data suggest that specific mannose oligosaccharides may activate as well as inhibit cellular immune responses at several different levels. These findings support the hypothesis that specific saccharide structures could participate in the physiologic regulation of the immune response.

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Authors and Affiliations

  1. Metabolism Branch, NCI, NIH, Bethesda, MD

    Neeraja Sathyamoorthy & Jean M. Decker

  2. Department of Biochemistry, University of Maine, Orono, ME, USA

    Anne P. Sherblom & Andrew Muchmore

Authors
  1. Neeraja Sathyamoorthy
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  2. Jean M. Decker
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  3. Anne P. Sherblom
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  4. Andrew Muchmore
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Sathyamoorthy, N., Decker, J.M., Sherblom, A.P. et al. Evidence that specific high mannose structures directly regulate multiple cellular activities. Mol Cell Biochem 102, 139–147 (1991). https://doi.org/10.1007/BF00234571

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  • DOI: https://doi.org/10.1007/BF00234571

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