eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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vol. 38

Toll-like receptors 3 ligation directly and indirectly affects mast cell cysteinyl leukotriene generation

Piotr Witczak
Anna Pietrzak
Aleksandra Słodka
Ewa Brzezińska-Błaszczyk

(Centr Eur J Immunol 2013; 38 (3): 343-348)
Online publish date: 2013/10/28
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Mast cells are numerously distributed throughout the body, but are particularly abundant beneath subepithelial layers of the skin, in the airways, gastrointestinal and genitourinary tracts, thus close to the external environment, virtually at the portals of infection. These cells express Toll-like receptors (TLRs) that detect bacteria-associated specific molecules. There are sparse data that mast cells have intracellular TLRs, such as TLR3, TLR7/8, and TLR9, recognizing virus-derived molecules. Thus, the aim of our study was to determine whether TLR3 ligand activates mast cells to degranulation and preformed mediator release as well as to cysteinyl leukotriene (cysLT) generation. The indirect effect of TLR3 ligation on IgE-mediated mast cell response was also examined. Experiments were carried out in vitro on isolated mature rat peritoneal mast cells and poly(I:C), a synthetic mimic of viral double-stranded (ds)RNA – TLR3 ligand, was used. Toll-like receptor 3 protein expression was assessed by western blot method. Poly(I:C)-induced mast cell degranulation was evaluated by histamine release by spectrofluorometric method, and cysLT generation and release was estimated by the ELISA test. We documented that native rat peritoneal mast cells constitutively express TLR3 protein. We also found that mast cells do not release histamine but generate and secrete cysLTs upon direct poly(I:C) stimulation. Mast cell priming with poly(I:C) has no effect on anti-IgE-induced histamine release. However, mast cell co-stimulation with poly(I:C) and anti-IgE causes a significant amplification of cysLT secretion. Our results suggest that dsRNA viruses could activate mast cells to proinflammatory mediator release and might affect severity of IgE-mediated allergic reactions.

mast cells, Toll-like receptors, anti-viral response, cysteinyl leukotrienes

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