Murakami Makoto, Taketomi Yoshitaka
Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; CREST, Japan Science and Technology Agency, Saitama, Japan.
Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Allergol Int. 2015 Jan;64(1):4-10. doi: 10.1016/j.alit.2014.07.005. Epub 2014 Oct 28.
Phospholipase A2s (PLA2s) are a group of enzymes that hydrolyze the sn-2 position of phospholipids to release (typically unsaturated) fatty acids and lysophospholipids, which serve as precursors for a variety of bioactive lipid mediators. Among the PLA2 superfamily, secreted PLA2 (sPLA2) enzymes comprise the largest subfamily that includes 11 isoforms with a conserved His-Asp catalytic dyad. Individual sPLA2 enzymes exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting their distinct biological roles. Recent studies using transgenic and knockout mice for individual sPLA2 isofoms have revealed their involvement in various pathophysiological events. Here, we overview the current state of knowledge about sPLA2s, specifically their roles in mast cells (MCs) in the context of allergology. In particular, we highlight group III sPLA2 (PLA2G3) as an "anaphylactic sPLA2" that promotes MC maturation and thereby anaphylaxis through a previously unrecognized lipid-orchestrated circuit.
磷脂酶A2(PLA2)是一类能水解磷脂sn-2位以释放(通常为不饱和)脂肪酸和溶血磷脂的酶,这些脂肪酸和溶血磷脂可作为多种生物活性脂质介质的前体。在PLA2超家族中,分泌型PLA2(sPLA2)酶是最大的亚家族,包括11种具有保守His-Asp催化二元组的亚型。单个sPLA2酶表现出独特的组织和细胞定位以及特定的酶学性质,这表明它们具有不同的生物学作用。最近使用针对单个sPLA2亚型的转基因和基因敲除小鼠进行的研究揭示了它们参与各种病理生理事件。在此,我们概述了关于sPLA2的当前知识状态,特别是它们在过敏学背景下在肥大细胞(MC)中的作用。我们特别强调III组sPLA2(PLA2G3)作为一种“过敏性sPLA2”,它通过一个以前未被认识的脂质调控回路促进MC成熟,从而引发过敏反应。