Saja Maha F, Baudino Lucie, Jackson William D, Cook H Terence, Malik Talat H, Fossati-Jimack Liliane, Ruseva Marieta, Pickering Matthew C, Woollard Kevin J, Botto Marina
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Renal and Vascular Inflammation Section, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Cell Rep. 2015 Sep 22;12(11):1802-15. doi: 10.1016/j.celrep.2015.08.020. Epub 2015 Sep 3.
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/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1(low) 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 Gr1(low) 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 Gr1(low) 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.
单核细胞是参与维持和恢复组织完整性的异质性效应细胞。然而，它们对高脂血症的反应仍知之甚少。在此，我们报告，在给予泊洛沙姆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Ly6C/Gr1（低）单核细胞的血液数量下降，而骨髓祖细胞数量保持相似。我们观察到Gr1（低）单核细胞在内皮界面的爬行和滞留增加，以及在多个器官中CD68（+）巨噬细胞的显著积聚。高甘油三酯血症伴随着组织表达增加，血浆CCL4和血液Gr1（低）单核细胞耗竭涉及百日咳毒素敏感受体轴。这些发现共同表明，富含甘油三酯的环境可改变血液单核细胞分布，促进Gr1（低）细胞的外渗。这些细胞对血脂异常的反应行为突出了高水平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。
