Emerging roles for lysophosphatidylserine in resolution of inflammation.
Emerging roles for lysophosphatidylserine in resolution of inflammation.
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DOI：
10.1016/j.plipres.2012.03.001
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发表时间：
2012-07
影响因子：
13.6
通讯作者：
Bratton DL
中科院分区：
文献类型：
--
作者：
Frasch SC;Bratton DL
尽管与其他磷脂重叠的结构方面，溶血磷脂酰丝氨酸（lysoPS），磷脂酰丝氨酸（二酰基PS）的单酰基衍生物，似乎发挥独特的信号传导特征，在启动急性炎症的早期阶段和在其解决的编排中都很重要。LysoPS长期以来被认为是肥大细胞生物学中的信号磷脂，显著增强受刺激的组胺释放和类花生酸产生。最近，由于在促进凋亡细胞的吞噬作用（所谓的吞噬作用）和炎症的消退中的新作用已经被鉴定，对lysoPS的兴趣重新抬头。关于后者，在活化或老化的凋亡中性粒细胞中/上产生的lysoPS通过经由巨噬细胞G蛋白偶联受体G2 A的信号传导增强它们被巨噬细胞的清除。在巨噬细胞中，这种早期作用途径通过增加PGE 2和cAMP的产生导致Rac 1活性的PKA依赖性增强。因此，用lysoPS刺激的巨噬细胞显示出清除大量急性炎症典型的募集的嗜中性粒细胞所必需的显著增加的巨噬细胞能力。鉴于这些细胞的清除对于组织功能的恢复至关重要，假设lysoPS作为促消退脂质介质在促进炎症的及时消退中发挥关键作用。本文将回顾我们目前对lysoPS生物学的认识，包括受体信号传导和产生机制，并总结其在炎症中扩大作用的最新证据。
Despite overlapping structural aspects with other phospholipids, lysophosphatidylserine (lysoPS), the monoacyl derivative of phosphatidylserine (diacylPS), appears to exert unique signaling characteristics important in both the early stages of initiating acute inflammation and in the orchestration of its resolution. LysoPS has long been known as a signaling phospholipid in mast cell biology, markedly enhancing stimulated histamine release and eicosanoid production. More recently, there has been a resurgence of interest in lysoPS as new roles in the promotion of phagocytosis of apoptotic cells, so-called efferocytosis, and resolution of inflammation have been identified. With regard to the latter, lysoPS generated in/on activated or aged apoptotic neutrophils enhances their clearance by macrophages via signaling through the macrophage G-protein coupled receptor G2A. In macrophages, this early acting pathway results in PKA-dependent augmentation of Rac1 activity via increased production of PGE2 and cAMP. As such, macrophages stimulated with lysoPS demonstrate significantly increased efferocytic capacity necessary to clear large numbers of recruited neutrophils typical of acute inflammation. Given that clearance of these cells is critical for restoration of tissue function, lysoPS, as a pro-resolving lipid mediator, is hypothesized to play a key role in promoting timely resolution of inflammation. This article will review our current knowledge of lysoPS biology including receptor signaling and mechanisms of generation as well as summarize the more recent evidence of its expanding roles in inflammation.
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