Apoptotic cells enhance sphingosine‐1‐phosphate receptor 1 dependent macrophage migration

Abstract

The lipid sphingosine-1-phosphate (S1P) is a chemokine for a variety of immune cells including lymphocytes and monocytes. Migration toward S1P is determined by the S1P receptor expression profile, with S1PR1/3 (where S1PR is S1P receptor) stimulating and S1PR2 attenuating migration. However, the impact and physiological significance of S1P-induced migration of macrophages is largely unclear. We observed that alternative activation of human macrophages, by IL-4 or apoptotic cells (ACs), enhanced S1PR1 expression. Moreover, ACs provoked macrophage migration toward S1P in an S1PR1-dependent manner as confirmed by pharmacological receptor inhibition and S1PR1-deficient murine macrophages. In a mouse model of resolving peritoneal inflammation, F4/80-driven deletion of S1PR1 reduced postinflammatory macrophage emigration from inflammatory sites. S1PR1 expression on macrophages might, therefore, be relevant for restoring tissue homeostasis during the resolution of inflammation. Keywords: Macrophage activation r Peritonitis r Resolution of inflammation r Sphingolipids r ZymosanAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMacrophages are innate immune cells that originate from primitive hematopoietic progenitors or blood-derived monocytes during inflammation [1]. Unlike resident macrophages, which largely regulate their numbers via local proliferation, mobilized monocytederived macrophages, like dendritic cells (DCs), rely on their high motility to extravasate tissues during inflammation. Resolution of inflammation requires clearance of monocyte-derived macrophages excess from the inflammation sites, which includes their migration to the lymphatic system [2]. The molecular mechanisms that guide macrophages toward the lymphatic system are unknown. One possible molecule involved in the process Correspondence: Dr. Bernhard Brüne e-mail: b.bruene@biochem.uni-frankfurt.de is sphingosine-1-phosphate (S1P). Detectable quantities of this sphingolipid are, at steady-state conditions, present only in blood and lymph of mammals [3]. Migration toward S1P is controlled by the relative expression of five specific S1P receptors (S1PR1-5), which are partially redundant in their cellular signaling capacity. S1P coupling to S1PR1 and S1PR3 favors migration, whereas S1PR2 counteracts this process [3].Mononuclear phagocytes express multiple S1PRs [4], which are species, cell type, and activation specific. Human monocytes express S1PR1, 2, and 4. Human macrophages express S1PR1-4 [5], while murine macrophages express mainly S1PR1 and 2 [6]. S1P plays a role in macrophage migration in physiology and pathophysiology [7]. In inflammatory settings, S1PR2 inhibited and * These authors contributed equally to this article.www.eji-journal.eu Eur. J. Immunol. 2013. 43: 3306-3313 Innate Immunity 3307 S1P3 promoted macrophage recruitment during thioglycollateinduced peritonitis as well as their motility in vitro [6,8]. During maturation, DCs change S1PR expression from S...

An update on the biology of sphingosine 1-phosphate receptors

“…This supports an earlier report that macrophage S1P 3 induces a pro-regenerative phenotype in a model of renal ischemia/reperfusion ( 106 ). A report utilizing the zymosan peritonitis model proposed that the resulting apoptotic neutrophils induced S1P 1 expression on recruited macrophages and that S1P 1 is necessary for emigration from the infl amed peritoneum, but has no role in efferocytosis or activation ( 107 ). S1P 2 on alveolar macrophages may regulate their phagocytic capacity, as S1pr2 Ϫ / Ϫ alveolar macrophages displayed decreased phagocytosis of the fungus Cryptococcus neoformans due to decreased expression of Fc receptors necessary for phagocytosis of antibody-opsonized fungus ( 108 ).…”

Sphingosine 1-Phosphate (S1P)/S1P Receptor2/3 Axis Promotes Inflammatory M1 Polarization of Bone Marrow-Derived Monocyte/Macrophage via G(α)i/o/PI3K/JNK Pathway

“…Besides, S1P acts as a crucial inflammatory mediator and can be released in response to inflammation and following injury [36,38]. Recent studies showed that S1P levels was markedly increased in acutely inflamed tissues and released by apoptotic cells [39]. Moreover, S1P level in serum was regarded as a prognostic factor [40].…”

Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration

“…In the present paper we could show that all S1P receptor subclasses were expressed on BMDM. Characterization of S1P expression patterns of macrophages has shown differing results, most likely due to the heterogeneity of macrophage populations used in different studies [17–21, 23, 34]. While expression of S1P 1 and S1P 2 could be consistently shown in murine and human macrophage populations, expression of the remaining three S1P receptor subclasses was reported more inconsistently.…”