Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 21 Αυγούστου 2017

Lipopolysaccharide suppresses IgE-mast cell mediated reactions

Abstract

Background

Clinical and experimental analyses have identified a central role for IgE/FcεRI/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, TLR-4-/- 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 expression of FcεRI on peritoneal MCs were quantitated.

Results

We show that LPS exposure of C57BL/6 WT mice constrains 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 FcεRI 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 FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression.

Conclusions & Clinical Relevance

Collectively, these studies suggest that LPS-induced IL-10 promotes the down regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10-pathway maybe used as a therapeutic approach to prevent adverse IgE-mediated reactions.

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