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


RESULTS
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-kappaB 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.


CONCLUSIONS
This is the first report of a synthetic polymer activating immune responses through TLR binding.
Department of Pathology, Albert Einstein College of Medicine, New York, New York, United States of America.
Radhashree
R
Maitra
Cristina C
CC
Clement
Giovanna M
GM
Crisi
Neil
N
Cobelli
Laura
L
Santambrogio
D000473:Alkanes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D011108:Polymers; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D051194:Toll-Like Receptor 1 / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D000473:Alkanes; D011108:Polymers; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2