Activation of human mast cells through the platelet-activating factor receptor
Activation of human mast cells through the platelet-activating factor receptor
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DOI：
10.1016/j.jaci.2010.01.056
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发表时间：
2010-05-01
影响因子：
14.2
通讯作者：
Okayama, Yoshimichi
中科院分区：
文献类型：
--
作者：
Kajiwara, Naoki;Sasaki, Tomomi;Okayama, Yoshimichi
背景：在人体内，过敏反应后血浆中的血小板激活因子(PAF)浓度显著升高，且与反应的严重程度密切相关。过敏反应中肥大细胞(MC)活化的全身性传播机制通常被认为与变应原的血源性传播有关，但这是不可信的，需要考虑放大机制。目的：我们研究了PAF诱导皮肤、肺和外周血(PB)来源的MC脱颗粒的能力，以及PB来源的MC对PAF激活的信号通路。方法：采用RT-PCR和Western印迹分析方法研究PAF受体的表达。通过分析不同抑制剂和磷脂酶C(PLC)mRNA沉默对PAF介导的组胺释放的影响，研究了PAF对PBMC释放组胺的影响。结果：首次发现PAF可以诱导人肺MCs和PBMCs释放组胺，但不能诱导皮肤MCs释放组胺。PAF受体偶联G(αI)的激活通过激活PLC-γ1和PLC-β2导致人巨噬细胞脱颗粒。PAF诱导的脱颗粒迅速，在5s时达到最大，并部分依赖于细胞外钙。结论：PAF在过敏反应的发生中介导了MC激活的扩增环。(《过敏与免疫杂志》2010；125：1137-45。)
Background: In human subjects platelet-activating factor (PAF) concentrations are markedly increased in the plasma after anaphylactic reactions, and these correlate strongly with the severity of the response. The mechanism for the systemic spread of mast cell (MC) activation in anaphylaxis is often assumed to relate to the hematogenous spread of allergen, but this is implausible, and amplification mechanisms need to be considered.Objective: We have investigated the ability of PAF to induce human MC degranulation using skin, lung, and peripheral blood (PB) derived cultured MCs and the signaling pathways activated in PB-derived MCs in response to PAF.Methods: The expression of PAF receptor was investigated by means of RT-PCR and Western blot analysis. Cell-signaling pathways in PB-derived MCs in response to PAF were investigated by analyzing the effect of various inhibitors and the silencing of phospholipase C (PLC) mRNA on PAF-mediated histamine release.Results: We show for the first time that PAF induces histamine release from human lung MCs and PB-derived MCs but not skin MCs. Activation of PAF receptor coupled G(alpha i) leads to degranulation through PLC gamma 1 and PLC beta 2 activation in human MCs. PAF-induced degranulation was rapid, being maximal at 5 seconds, and was partially dependent on extracellular Ca2+.Conclusion: Our findings provide a mechanism whereby PAF mediates an amplification loop for MC activation in the generation of anaphylaxis. (J Allergy Clin Immunol 2010;125:1137-45.)