The modulation of dendritic cell integrin binding and activation by RGD-peptide density gradient substrates

Abhinav P. Acharya, Natalia V. Dolgova, Nicole M. Moore, Chang Qing Xia, Michael J. Clare-Salzler, Matthew L. Becker, Nathan D. Gallant, Benjamin G. Keselowsky

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Dendritic cells (DCs) are central regulators of the immune system that operate in both innate and adaptive branches of immunity. Activation of DC by numerous factors, such as danger signals, has been well established. However, modulation of DC functions through adhesion-based cues has only begun to be characterized. In this work, DCs were cultured on surfaces presenting a uniform gradient of the integrin-targeting RGD peptide generated using the recently established " universal gradient substrate for click biofunctionalization" methodology. Surface expression of activation markers (costimulatory molecule CD86 and stimulatory molecule MHC-II) and production of cytokines IL-10 and IL-12p40 of adherent DCs was quantified in situ. Additionally, bound αV integrin was quantified in situ using a biochemical crosslinking/extraction method. Our findings demonstrate that DCs upregulated CD86, MHC-II, IL-10, IL-12p40 and αV integrin binding as a function of RGD surface density, with production of IL-12p40 being the marker most sensitive to RGD surface density. Surface expression of activation markers demonstrated moderate correlation with αV integrin binding, while cytokine production was highly correlated with αV integrin binding. This work demonstrates the utility of the surface density gradient platform as a high-throughput method to investigate RGD density-dependent DC adhesive responses. Furthermore, this quantitative analysis of DC integrin-based activation represents a first of its type, helping to establish the field of adhesion-based modulation of DCs as a general mechanism that has previously not been defined, and informs the rational design of biomimetic biomaterials for immunomodulation.

Original languageEnglish (US)
Pages (from-to)7444-7454
Number of pages11
JournalBiomaterials
Volume31
Issue number29
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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Mice (computer peripherals)
CD86 Antigens
Interleukin-12 Subunit p40
Immunology
Activation analysis
Activation Analysis
Dendrimers
Oligopeptides
Biomimetics
Machine design
Histocompatibility Antigens Class II
Cell adhesion
Allergy and Immunology
Inbred C57BL Mouse
Cell Adhesion
Integrins
Interleukin-10
Biological materials
Dendritic Cells
Peptides

Keywords

  • Biomimetic
  • Cell adhesion
  • Dendritic cell
  • High-throughput
  • Immune response
  • RGD peptide

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Acharya, A. P., Dolgova, N. V., Moore, N. M., Xia, C. Q., Clare-Salzler, M. J., Becker, M. L., ... Keselowsky, B. G. (2010). The modulation of dendritic cell integrin binding and activation by RGD-peptide density gradient substrates. Biomaterials, 31(29), 7444-7454. https://doi.org/10.1016/j.biomaterials.2010.06.025

The modulation of dendritic cell integrin binding and activation by RGD-peptide density gradient substrates. / Acharya, Abhinav P.; Dolgova, Natalia V.; Moore, Nicole M.; Xia, Chang Qing; Clare-Salzler, Michael J.; Becker, Matthew L.; Gallant, Nathan D.; Keselowsky, Benjamin G.

In: Biomaterials, Vol. 31, No. 29, 01.10.2010, p. 7444-7454.

Research output: Contribution to journalArticle

Acharya, AP, Dolgova, NV, Moore, NM, Xia, CQ, Clare-Salzler, MJ, Becker, ML, Gallant, ND & Keselowsky, BG 2010, 'The modulation of dendritic cell integrin binding and activation by RGD-peptide density gradient substrates', Biomaterials, vol. 31, no. 29, pp. 7444-7454. https://doi.org/10.1016/j.biomaterials.2010.06.025
Acharya, Abhinav P. ; Dolgova, Natalia V. ; Moore, Nicole M. ; Xia, Chang Qing ; Clare-Salzler, Michael J. ; Becker, Matthew L. ; Gallant, Nathan D. ; Keselowsky, Benjamin G. / The modulation of dendritic cell integrin binding and activation by RGD-peptide density gradient substrates. In: Biomaterials. 2010 ; Vol. 31, No. 29. pp. 7444-7454.
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