Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators
Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators
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DOI：
10.1182/blood-2012-04-423525
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发表时间：
2012-10-11
期刊：
影响因子：
20.3
通讯作者：
Serhan, Charles N.
中科院分区：
文献类型：
--
作者：
Dalli, Jesmond;Serhan, Charles N.
吞噬细胞协调急性炎症和宿主防御。在这里，我们进行了脂质介体(LM)代谢类脂组学研究，分析了不同的吞噬细胞：中性粒细胞(PMN)、凋亡的PMN和巨噬细胞。巨噬细胞吞噬增加了专化的前分解介质(SPM)的生物合成，包括Resolvin D1(RvD1)、RvD2和RvE2，PMN微粒进一步促进了这些生物合成。而酵母多糖刺激的PMN主要表现为白三烯B-4和20-OH-白三烯B-4，以及脂氧素标志物5，15-diHETE。用氚标记的前体(d(8)-花生四烯酸、d(5)-二十碳五烯酸和d(5)-二十二碳六烯酸)，我们发现在胞吐过程中，凋亡的PMN和微粒参与了SPM的生物合成。M_2巨噬细胞产生SPM，包括M-树脂-1(299+/-8vs45+/-6PG/2.5+/-10(5)个细胞；P<；.01)以及比M_1更少的白三烯B-4和前列腺素。这两种巨噬细胞亚型的凋亡PMN摄取导致了它们的LM谱的调节。M2中白三烯B-4表达下调(668+/-81vs351+/-39pg/2.5+/-10(5)细胞；P<；0.01)，而包括脂氧素A(4)在内的SPM表达增加(977+/-173vs675+/-167pg/2.5+/-10(5)细胞；P<；0.05)。相反，M2巨噬细胞对凋亡的PMN的摄取减少(类似于25%)。总之，这些结果建立了人类吞噬细胞和相关亚群的LM特征图谱。此外，它们还提供了在急性炎症过程的特定阶段中对特定内源性LM的微粒子调节及其在人类原代吞噬细胞中的动态变化的证据。(血。2012年；120(15)：E60-E72)
Phagocytes orchestrate acute inflammation and host defense. Here we carried out lipid mediator (LM) metabololipidomics profiling distinct phagocytes: neutrophils (PMN), apoptotic PMN, and macrophages. Efferocytosis increased specialized pro-resolving mediator (SPM) biosynthesis, including Resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles. Apoptotic PMN gave elevated prostaglandin E-2, lipoxin B-4 and RvE2, whereas zymosan-stimulated PMN showed predominantly leukotriene B-4 and 20-OH-leukotriene B-4, as well as lipoxin marker 5,15-diHETE. Using deuteriumlabeled precursors (d(8)-arachidonic acid, d(5)-eicosapentaenoic acid, and d(5)-docosahexaenoic acid), we found that apoptotic PMN and microparticles contributed to SPM biosynthesis during efferocytosis. M2 macrophages produced SPM including maresin-1 (299 +/- 8vs45 +/- 6 pg/2.5 +/- 10(5) cells; P < .01) and lower amounts of leukotriene B-4 and prostaglandin than M1. Apoptotic PMN uptake by both macrophage subtypes led to modulation of their LM profiles. Leukotriene B-4 was down-regulated in M2 (668 +/- 81 vs 351 +/- 39 pg/2.5 +/- 10(5) cells; P < .01), whereas SPM including lipoxin A(4) (977 +/- 173 vs 675 +/- 167 pg/2.5 +/- 10(5) cells; P < .05) were increased. Conversely, uptake of apoptotic PMN by M2 macrophages reduced (similar to 25%) overall LM. Together, these results establish LM signature profiles of human phagocytes and related subpopulations. Moreover, they provide evidence for microparticle regulation of specific endogenous LM during defined stages of the acute inflammatory process and their dynamic changes in human primary phagocytes. (Blood. 2012; 120(15): e60-e72)