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Author Notes:

Julia E. Babensee, Wallace H. Coulter Dept. of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA, julia.babensee@bme.gatech.edu

We would like to acknowledge Dr. Xuezheng Song from Emory University for his invaluable expertise with glycan isolation and functionalization.

Also we would like to thank David Smith for the generous contribution of AEAB, mass spectrometer, and lab space.

Subjects:

Research Funding:

We also wish to acknowledge the Consortium for Functional Glycomics; and NIH Grants GM62116 and GM098791 for contributing glycans and other resources.

We would like to acknowledge support through the NIH Cell and Tissue Engineering Doctoral Training Grant and through the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454, research supported by NIH 1RO1EB004633-01A1, 1R21EB012339-01A1.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Glycoconjugates
  • Dendritic cells
  • High throughput
  • Immunomodulation
  • THY-1-NEGATIVE MUTANT LYMPHOMAS
  • LIPID-LINKED OLIGOSACCHARIDES
  • ANTIGEN-PRESENTING CELLS
  • RECEPTORS DC-SIGN
  • IMMUNE-RESPONSES
  • LECTIN RECEPTORS
  • GENE DELIVERY
  • T-CELLS
  • MANNOSE
  • MICROARRAYS

Molecular factors in dendritic cell responses to adsorbed glycoconjugates

Tools:

Journal Title:

Biomaterials

Volume:

Volume 35, Number 22

Publisher:

, Pages 5862-5874

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Carbohydrates and glycoconjugates have been shown to exert pro-inflammatory effects on the dendritic cells (DCs), supporting pathogen-induced innate immunity and antigen processing, as well as immunosuppressive effects in the tolerance to self-proteins. Additionally, the innate inflammatory response to implanted biomaterials has been hypothesized to be mediated by inflammatory cells interacting with adsorbed proteins, many of which are glycosylated. However, the molecular factors relevant for surface displayed glycoconjugate modulation of dendritic cell (DC) phenotype are unknown. Thus, in this study, a model system was developed to establish the role of glycan composition, density, and carrier cationization state on DC response. Thiol modified glycans were covalently bound to a model protein carrier, maleimide functionalized bovine serum albumin (BSA), and the number of glycans per BSA modulated. Additionally, the carrier isoelectric point was scaled from a pI of ~4.0 to ~10.0 using ethylenediamine (EDA). The DC response to the neoglycoconjugates adsorbed to wells of a 384-well plate was determined via a high throughput assay. The underlying trends in DC phenotype in relation to conjugate properties were elucidated via multivariate general linear models. It was found that glycoconjugates with more than 20 glycans per carrier had the greatest impact on the pro-inflammatory response from DCs, followed by conjugates having an isoelectric point above 9.5. Surfaces displaying terminal α1-2 linked mannose structures were able to increase the inflammatory DC response to a greater extent than did any other terminal glycan structure. The results herein can be applied to inform the design of the next generation of combination products and biomaterials for use in future vaccines and implanted materials.

Copyright information:

© 2014 Elsevier Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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