Immunogenecity of modified alkane polymers is mediated through TLR1/2 activation

Radhashree Maitra, Cristina C. Clement, Giovanna M. Crisi, Neil J. Cobelli, Laura Santambrogio

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: With the advancement of biomedical technology, artificial materials have been developed to replace diseased, damaged or nonfunctional body parts. Among such materials, ultra high molecular weight alkane or modified alkyl polymers have been extensively used in heart valves, stents, pacemakers, ear implants, as well as total joint replacement devices. Although much research has been undertaken to design the most non-reactive biologically inert polyethylene derivatives, strong inflammatory responses followed by rejection and failure of the implant have been noted. Methodology/Principal Findings: Purification of the alkane polymers from the site of inflammation revealed extensive "in vivo" oxidation as detected by fourier transformed infra-red spectroscopy. Herein, we report the novel observation that oxidized alkane polymers induced activation of TLR1/2 pathway as determined by ligand dependent changes in intrinsic tyrosine fluorescence intensity and NF-κB luciferase gene assays. Oxidized polymers were very effective in activating dendritic cells and inducing secretion of pro-inflammatory cytokines. Molecular docking of the oxidized alkanes designated ligand specificity and polymeric conformations fitting into the TLR1/2 binding grooves. Conclusion/Significance: This is the first report of a synthetic polymer activating immune responses through TLR binding.

Original languageEnglish (US)
Article numbere2438
JournalPLoS One
Volume3
Issue number6
DOIs
StatePublished - Jun 18 2008

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Alkanes
alkanes
polymers
Polymers
Chemical activation
Replacement Arthroplasties
inflammation
heart valves
Ligands
Pacemakers
Biomedical Technology
Stents
Heart Valves
infrared spectroscopy
Polyethylene
luciferase
dendritic cells
Luciferases
Human Body
polyethylene

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Immunogenecity of modified alkane polymers is mediated through TLR1/2 activation. / Maitra, Radhashree; Clement, Cristina C.; Crisi, Giovanna M.; Cobelli, Neil J.; Santambrogio, Laura.

In: PLoS One, Vol. 3, No. 6, e2438, 18.06.2008.

Research output: Contribution to journalArticle

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