Lipopolysaccharide suppresses IgE-mast cell mediated reactions
| Autor: | Nianrong Wang, Simone Vanoni, Simon P. Hogan, Jörg Köhl, Melanie C. McKell, Lisa Waggoner, Andrew T. Dang, Taeko K. Noah, David Wu, Senad Divanovic, Amnah Yamani, Anna Kordowski, Kasper Hoebe |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Lipopolysaccharide medicine.medical_treatment Immunology Cell Immunoglobulin E Article Cell Degranulation 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Immunology and Allergy Animals Mast Cells Anaphylaxis Desensitization (medicine) Mice Knockout biology Chemistry Receptors IgE medicine.disease Mast cell Interleukin-10 Toll-Like Receptor 4 Serum cytokine Disease Models Animal 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Hematocrit biology.protein Macrophages Peritoneal Tumor necrosis factor alpha Calcium 030215 immunology Signal Transduction |
| Popis: | SummaryBackground Clinical and experimental analyses have identified a central role for IgE/FceRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis. Objective We examined the effect of LPS exposure on the induction of IgE-mast cell (MC) mediated reactions in mice. Methods C57BL/6 WT, tlr4−/− and IL10−/− mice were exposed to LPS, and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE, and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca2+-mobilization and the expression of FceRI on peritoneal MCs were quantitated. Results We show that LPS exposure of C57BL/6 WT mice constraints IgE-MC–mediated reactions. LPS-induced suppression of IgE-MC–mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FceRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short term with MC sensitivity to IgE reconstituted within 48 hours, which was associated with recapitulation of FceRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FceRI surface expression. Conclusions & Clinical Relevance Collectively, these studies suggest that LPS-induced IL-10 promotes the down-regulation of MC surface FceRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10 pathway may be used as a therapeutic approach to prevent adverse IgE-mediated reactions. |
| Databáze: | OpenAIRE |
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