Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.
Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.
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DOI：
10.1016/j.celrep.2015.08.020
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发表时间：
2015-09-22
期刊：
影响因子：
8.8
通讯作者：
Botto M
中科院分区：
文献类型：
--
作者：
Saja MF;Baudino L;Jackson WD;Cook HT;Malik TH;Fossati-Jimack L;Ruseva M;Pickering MC;Woollard KJ;Botto M
单核细胞是参与维持和恢复组织完整性的异质效应细胞。然而，它们对高脂血症的反应仍然知之甚少。在这里，我们报告了在泊洛沙姆407诱导的富含甘油三酯的脂蛋白水平升高的情况下，非经典的Ly6C/Gr1低单核细胞的血液数量下降，而骨髓前体细胞的数量保持不变。我们观察到Gr1low单核细胞在内皮界面的爬行和滞留增加，CD68+巨噬细胞在几个器官中显著聚集。高甘油三酯血症伴有组织表达增加，血浆CCL4和血中单核细胞减少与百日咳毒素敏感的受体轴有关。总而言之，这些发现表明，富含甘油三酯的环境可以改变血液中单核细胞的分布，促进Gr1低细胞的外渗。这些细胞对血脂异常的反应突出了高水平的富含甘油三酯的脂蛋白可能对先天免疫细胞产生的重大影响。高甘油三酯血症促进Gr1外渗低单核细胞CD68+组织巨噬细胞聚集在没有明显炎症的情况下高甘油三酯血症与CCl4水平升高有关CCl4参与了Gr1低单核细胞的迁移高水平的富含甘油三酯的脂蛋白参与了心血管并发症的发病。Saja等人。证明高甘油三酯血症促进单核细胞外渗和组织巨噬细胞聚集。高甘油三酯血症与CCl4水平升高有关，CCl4有助于Gr1低单核细胞的迁移。
Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1low monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1low monocytes at the endothelial interface and a marked accumulation of CD68+ macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1low monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1low cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells. Hypertriglyceridemia promotes the extravasation of Gr1low monocytes CD68+ tissue macrophages accumulate in the absence of overt inflammation Hypertriglyceridemia is associated with increased CCL4 levels CCL4 is involved in the migration of Gr1low monocytes High levels of triglyceride-rich lipoproteins have been implicated in the pathogenesis of cardiovascular complications. Saja et al. demonstrate that hypertriglyceridemia promotes extravasation of Gr1low monocytes and accumulation of tissue macrophages. Hypertriglyceridemia was associated with increased levels of CCL4, which contributes to the migration of Gr1low monocytes.