IgE-dependent sensitization increases responsiveness to LPS but does not modify development of endotoxin tolerance in mast cells.
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.
Medina-Tamayo
Jaciel
J
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, Sede Sur, Calzada de los Tenorios No 235, Col Granjas Coapa, Tlalpan, Mexico, DF, México.
Ibarra-Sánchez
Alfredo
A
Padilla-Trejo
Alejandro
A
González-Espinosa
Claudia
C
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D051550:I-kappa B Kinase / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles; D013450:Sulfones; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
C416282:BAY 11-7085; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D051550:I-kappa B Kinase