FcεR1-mediated mast cell reactivity is amplified through prolonged Toll-like receptor-ligand treatment.
FcεR1-mediated mast cell reactivity is amplified through prolonged Toll-like receptor-ligand treatment.
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DOI：
10.1371/journal.pone.0043547
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Adner M
中科院分区：
文献类型：
--
作者：
Saluja R;Delin I;Nilsson GP;Adner M
肥大细胞衍生的介质介导了哮喘的几个病理特征。微生物感染导致哮喘加重，肥大细胞在其中的作用仍然无法理解。在本研究中，我们研究了Toll样受体(TLRs)1-9的特征表达模式以及TLR配体处理对IgE受体介导的肥大细胞反应性的影响。在这项研究中，我们使用了体外分化的结缔组织，如肥大细胞(CTLMC)和粘膜样肥大细胞(MLMC)。两种表型分别用TLR1/2、TLR2/6、TLR3和TLR4配体处理24 h或96 h，然后用IgE和抗原激活。在IgE受体激活后，与TLR配体长时间接触(96h)可促进肥大细胞的反应性。在CTLMC和MLMC中，用脂多糖激活TLR4的作用最为明显，可促进白三烯、细胞因子和趋化因子的脱颗粒和分泌。内毒素的作用是通过MyD88依赖的途径介导的，而增强效应则涉及JNK依赖的途径。我们发现，肥大细胞对病原体/TLR配体的长期暴露通过使它们在随后被IgE受体激活时增加几种炎症介质的释放来调节它们的效应器反应。这些数据表明，感染可能通过促进肥大细胞释放介质而夸大过敏反应的严重程度，例如哮喘。
Mast cell-derived mediators mediate several of the pathological features of asthma. Microbial infections induce asthma exacerbations in which the contribution of mast cells remains incomprehensible. In this study we have investigated the characteristic expression pattern of Toll-like receptors (TLRs) 1–9 and the effect of TLR ligand treatment on IgE-receptor mediated mast cell reactivity. For the studies we employed in vitro differentiated connective tissue like mast cells (CTLMC) and mucosal like mast cells (MLMC) from mice. Both phenotypes were treated for 24 h or 96 h with ligands for TLR1/2, TLR2/6, TLR3 and TLR4, before activation with IgE and antigen. Prolonged exposure (96 h) with TLR-ligands promoted mast cell reactivity following IgE-receptor activation. TLR4 activation with LPS generated the most pronounced effect, with an enhanced degranulation and secretion of leukotrienes, cytokines and chemokines, in both CTLMC and MLMC. The effect of LPS was mediated through a Myd88-dependent pathway and the increased effect involved JNK-dependent pathway. We find that prolonged exposure of mast cells to pathogens/TLR-ligands modulates their effector responses by priming them for increased release of several inflammatory mediators when subsequently activated by IgE-receptors. These data suggest that infections might exaggerate the severity of allergic reactions such as in asthma, by enhancing mediator release from mast cells.
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影响因子：
5.5
作者：
Farhat, Katja;Riekenberg, Sabine;Ulmer, Artur J.
通讯作者：
Ulmer, Artur J.
DOI：
10.1164/ajrccm.159.3.9801052
发表时间：
1999-03-01
影响因子：
24.7
作者：
Rakes, CP;Arruda, E;Heymann, PW
通讯作者：
Heymann, PW
DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
15.9
作者：
CALHOUN, WJ;DICK, EC;BUSSE, WW
通讯作者：
BUSSE, WW
影响因子：
10
作者：
Murray, CS;Poletti, G;Custovic, A
通讯作者：
Custovic, A