Polymyxin B enhances ISS-mediated immune responses across multiple species.
Cell Immunol
; 229(2): 93-105, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15474524
ABSTRACT
The immunostimulatory effects of bacterial DNA on mammalian cells have been localized to unmethylated CpG motifs, and synthetic CpG-containing oligodeoxynucleotides that mimic these effects are known as immunostimulatory sequences (ISS). We have found that the polycationic antibiotic, polymyxin B (PMXB), associates with ISS and serum albumin in vitro and forms microparticles that greatly increase the activity of ISS on plasmacytoid dendritic cells (PDCs). Specifically, ISS/PMXB greatly enhanced IFN-alpha production from PDCs and other activities downstream of IFN-alpha, including IFN-gamma secretion, NK lytic activity, and the expression of genes dependent upon IFN-alpha/IFN-gamma. This amplification was specific for the IFN-alpha pathway since other ISS activities, including B cell proliferation, B cell IL-6 secretion, and PDC maturation, were not affected by PMXB. Both the polycationic peptide and lipophilic fatty acid side chain domains of PMXB, as well as the presence of a third party stabilizing agent such as albumin or Tween 85, were required for particle formation and enhanced ISS activity. The ISS-enhancing activity of PMXB was observed across multiple species (human, primate, and mouse) and in vivo (primate, mouse). These data illustrate the usefulness of formulating ISS with a cationic lipopeptide such as PMXB, which focuses and greatly amplifies the ISS-induced pathway of IFN-alpha-mediated responses.
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Base de dados:
MEDLINE
Assunto principal:
Oligodesoxirribonucleotídeos
/
Polimixina B
/
Antibacterianos
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article