IgE-dependent sensitization increases responsiveness to LPS but does not modify development of endotoxin tolerance in mast cells

Inflamm Res. 2011 Jan;60(1):19-27. doi: 10.1007/s00011-010-0230-4. Epub 2010 Jul 13.

Abstract

Objective: Effects of immunoglobulin E (IgE)-dependent sensitization on the response to bacterial lipopolysaccharide (LPS) were analyzed in mast cells.

Methods: Murine bone marrow-derived mast cells (BMMCs) were sensitized or not with IgE before stimulation with LPS. TLR4 and co-receptors expression was analyzed by flow cytometry and RT-PCR, TNF-α production by ELISA, IKK and IκB activation by western blot or immunoprecipitation. NFκB nuclear translocation was determined by EMSA.

Results: IgE-sensitized BMMCs secreted larger amounts of TNF-α than non-sensitized cells shortly after LPS challenge. No change in TLR4, CD14 or MD-2 expression was detected after the IgE-dependent sensitization process, whereas TLR4-dependent phosphorylation of IKK and IκB was augmented. IgE-dependent sensitization increased basal NFκB activity. Endotoxin tolerance was not affected by the IgE-dependent sensitization process.

Conclusions: IgE-induced sensitization primes mast cells for higher response to LPS through pre-activation of NFκB transcription factor. IgE-dependent sensitization does not modify events leading to endotoxin tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Cells, Cultured
  • I-kappa B Kinase / metabolism
  • Immune Tolerance / immunology*
  • Immunoglobulin E / immunology*
  • Lipopolysaccharides / immunology*
  • Lipopolysaccharides / pharmacology
  • Mast Cells / cytology
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitriles
  • Sulfones
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • BAY 11-7085
  • Lipopolysaccharides
  • NF-kappa B
  • Nitriles
  • Sulfones
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Immunoglobulin E
  • I-kappa B Kinase