PMID- 20637504
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20171116
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 31
IP  - 29
DP  - 2010 Oct
TI  - The modulation of dendritic cell integrin binding and activation by RGD-peptide 
      density gradient substrates.
PG  - 7444-54
LID - 10.1016/j.biomaterials.2010.06.025 [doi]
AB  - 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 alpha(V) 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 
      alpha(V) 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 alpha(V) 
      integrin binding, while cytokine production was highly correlated with alpha(V) 
      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.
CI  - Published by Elsevier Ltd.
FAU - Acharya, Abhinav P
AU  - Acharya AP
AD  - Materials Science and Engineering, University of Florida, Gainesville, FL, USA.
FAU - Dolgova, Natalia V
AU  - Dolgova NV
FAU - Moore, Nicole M
AU  - Moore NM
FAU - Xia, Chang-Qing
AU  - Xia CQ
FAU - Clare-Salzler, Michael J
AU  - Clare-Salzler MJ
FAU - Becker, Matthew L
AU  - Becker ML
FAU - Gallant, Nathan D
AU  - Gallant ND
FAU - Keselowsky, Benjamin G
AU  - Keselowsky BG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100716
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (B7-2 Antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Integrins)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Oligopeptides)
RN  - 130068-27-8 (Interleukin-10)
RN  - 78VO7F77PN (arginyl-glycyl-aspartic acid)
SB  - IM
MH  - Animals
MH  - B7-2 Antigen/metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Integrins/*metabolism
MH  - Interleukin-10/metabolism
MH  - Interleukin-12 Subunit p40/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligopeptides/*pharmacology
EDAT- 2010/07/20 06:00
MHDA- 2010/11/17 06:00
CRDT- 2010/07/20 06:00
PHST- 2010/04/28 00:00 [received]
PHST- 2010/06/15 00:00 [accepted]
PHST- 2010/07/20 06:00 [entrez]
PHST- 2010/07/20 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
AID - S0142-9612(10)00773-8 [pii]
AID - 10.1016/j.biomaterials.2010.06.025 [doi]
PST - ppublish
SO  - Biomaterials. 2010 Oct;31(29):7444-54. doi: 10.1016/j.biomaterials.2010.06.025. 
      Epub 2010 Jul 16.