title: Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.
abstract: Introduction. 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 (S1P1-5) 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.Methods. 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.Results. All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. 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.Discussion. The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.
authors.affiliation: Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Müller
authors.affiliation: Department of Vascular Surgery, Krankenhaus Ludmillenstift, Ludmillenstraße 4-6, 49716 Meppen, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: von Bernstorff
authors.affiliation: Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany.
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Heidecke
authors.affiliation: Department of General Surgery, Visceral, Thoracic and Vascular Surgery, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany.
authors.forename: Tobias
authors.identifier: 0000-0001-8602-8431
authors.initials: T
authors.lastname: Schulze
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics*; D010587:Phagocytosis / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis / Q000235:genetics*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016207:Cytokines; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013110:Sphingosine