Department of Lipid Life Science, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jan;1870(1):159563. doi: 10.1016/j.bbalip.2024.159563. Epub 2024 Sep 25.
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.
血小板激活因子（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关键作用。在过敏领域，先前的研究表明，PAF 是对外界刺激的反应产生的，并通过 PAF 受体（PAFR）促进过敏反应。然而，内源性 PAF 的来源及其体内病理生理动力学在很大程度上仍不清楚。在这里，我们报告说，快速和局部的 PAF 生成完全依赖于 IgE 介导的被动皮肤过敏反应中肥大细胞中表达的溶血磷脂酰基转移酶 9（LPLAT9，也称为 LPCAT2）。然而，我们发现 LPLAT9 敲除（KO）小鼠并没有显示出血管渗漏减弱。此外，在该模型中，PAFR KO 小鼠的血管渗漏减少，但内皮细胞特异性小鼠则没有。这些差异突出表明在病理生理过程中，PAF 和 PAFR 的生物学功能仍然存在尚未解决的复杂性。
