Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
Arch Immunol Ther Exp (Warsz). 2011 Jun;59(3):195-201. doi: 10.1007/s00005-011-0123-4. Epub 2011 Apr 10.
Phosphatidylserine (PS), which is normally located on the inner leaflet of the plasma membrane, translocates to the outer leaflet at the early stage of apoptosis. The PS externalization provides a signal for phagocytes to initiate uptake of apoptotic cells. After phagocytosis of apoptotic cells, phagocytes induce the secretion of anti-inflammatory mediators including prostaglandin E(2) (PGE(2)). PS-containing liposomes (PSLs) can mimic the effects of apoptotic cells on phagocytes to induce the secretion of PGE(2). PSLs induce the PGE(2) secretion from microglia without induction of either cyclooxygenase (COX)-2 or microsomal prostaglandin E synthase (mPGES)-1. PSLs are found to rather utilize COX-1/mPGES-2 system to produce PGE(2) secretion and then shift microglia and macrophages from pro- to anti-inflammatory phenotype by an autocrine action of PGE(2). Moreover, PSLs inhibit the maturation of dendritic cells and osteoclast precursors. Therefore, PSLs will be potential pharmacological interventions for inflammatory and immune diseases through feedback mechanism utilizing PGE(2).
磷脂酰丝氨酸（PS）通常位于质膜的内小叶，在细胞凋亡的早期向质膜外小叶易位。PS 的外排为吞噬细胞启动吞噬凋亡细胞提供了信号。吞噬凋亡细胞后，吞噬细胞诱导包括前列腺素 E2（PGE2）在内的抗炎介质的分泌。载有 PS 的脂质体（PSLs）可以模拟凋亡细胞对吞噬细胞的作用，诱导 PGE2 的分泌。PSLs 诱导小胶质细胞分泌 PGE2 而不诱导环氧化酶（COX）-2 或微粒体前列腺素 E 合酶（mPGES）-1。PSLs 被发现利用 COX-1/mPGES-2 系统产生 PGE2 分泌，然后通过 PGE2 的自分泌作用将小胶质细胞和巨噬细胞从促炎表型转变为抗炎表型。此外，PSLs 抑制树突状细胞和破骨细胞前体的成熟。因此，PSLs 将通过利用 PGE2 的反馈机制成为治疗炎症和免疫性疾病的潜在药物干预措施。
