重新评估皮肤过敏性休克的典型 PAF 通路。

IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Tomoyuki Suzuki , Yoshitaka Taketomi , Keisuke Yanagida , Tomomi Yoshida-Hashidate , Takahide Nagase , Makoto Murakami , Takao Shimizu , Hideo Shindou
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引用次数: 0

摘要

血小板活化因子(PAF)是一种强效的经典脂质介质,在过敏和神经系统疾病等多种疾病中发挥着至关重要的作用。在过敏领域,先前的研究表明 PAF 是在对细胞外刺激做出反应时产生的,并通过 PAF 受体(PAFR)促成过敏反应。然而,内源性 PAF 的来源及其在体内的病理生理动态在很大程度上仍然难以捉摸。在这里,我们报告了在 IgE 介导的被动皮肤过敏性休克中,局部 PAF 的快速生成完全依赖于肥大细胞中表达的溶血磷脂酰基转移酶 9(LPLAT9,又称 LPCAT2)。然而,我们发现 LPLAT9 基因敲除(KO)小鼠的血管渗漏并没有减少。此外,在该模型中,PAFR KO 小鼠的血管渗漏减少,而内皮细胞特异性小鼠则没有。这些分歧凸显了 PAF 和 PAFR 在病理生理过程中的生物功能的复杂性,而这一复杂性尚未得到解决。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Re-evaluation of the canonical PAF pathway in cutaneous anaphylaxis
Platelet-activating factor (PAF) is a potent classical lipid mediator that plays a critical role in various diseases such as allergy and nervous system disorders. In the realm of allergy, previous studies suggested that PAF is generated in response to extracellular stimuli and contributes to allergic reactions via PAF receptor (PAFR). However, the sources of endogenous PAF and its pathophysiological dynamics remain largely elusive in vivo. Here, we report that rapid and local PAF generation completely depends on lysophospholipid acyltransferase 9 (LPLAT9, also known as LPCAT2) expressed in mast cells in IgE-mediated passive cutaneous anaphylaxis. However, we found that LPLAT9 knockout (KO) mice did not display attenuated vascular leakage. Additionally, decreased vascular leakage was observed in PAFR KO mice, but not in endothelial cell-specific mice in this model. These divergences highlight a yet unsolved complexity of the biological functions of PAF and PAFR in a pathophysiological process.
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来源期刊
CiteScore
11.00
自引率
2.10%
发文量
109
审稿时长
53 days
期刊介绍: BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.
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