Müller Jan, von Bernstorff Wolfram, Heidecke Claus-Dieter, Schulze Tobias
Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany.
Department of Vascular Surgery, Krankenhaus Ludmillenstift, Ludmillenstraße 4-6, 49716 Meppen, Germany.
Biomed Res Int. 2017;2017:7584621. doi: 10.1155/2017/7584621. Epub 2017 Mar 6.
. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P. In contrast, M1-polarized macrophages significantly downregulated S1P. The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.
巨噬细胞是复杂生物过程中的关键参与者。响应环境信号，巨噬细胞会向促炎（M1）或抗炎（M2）表型极化。鞘氨醇-1-磷酸（S1P）是一种生物活性溶血磷脂，它通过5种G蛋白偶联受体（S1P）发挥作用，以影响广泛的生物过程。本研究评估了M1和M2极化前后巨噬细胞上S1P受体的表达，并对巨噬细胞两种激活状态下的S1P信号传导进行了比较分析。来自C57 BL/6小鼠的骨髓源性巨噬细胞（BMDM）在M1或M2极化条件下培养。通过定量RT-PCR测定S1P受体的表达。在体外评估S1P对巨噬细胞激活、迁移、吞噬作用和细胞因子分泌的影响。所有5种S1P受体亚类均在巨噬细胞中表达。在M1和M2极化条件下培养均导致S1P的显著下调。相比之下，M1极化的巨噬细胞显著下调S1P。其余三种S1P受体的表达没有变化。在M2极化条件下，S1P增加了诱导型一氧化氮合酶（iNOS）的表达。此外，S1P诱导M1巨噬细胞的趋化作用，并改变M2巨噬细胞中的细胞因子产生。吞噬作用不受S1P信号传导的影响。不同特异性S1P受体谱的表达可能为选择性影响M1或M2极化巨噬细胞提供一种可能性。
