Regulation of macrophage function by sphingosine-1-phosphate

Weigert, Andreas; Weis, Nicole; Brüne, Bernhard

doi:10.1016/j.imbio.2009.06.003

Cited by 97 publications

(70 citation statements)

References 117 publications

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“…45 An S1P 1 -selective agonist may act directly on macrophage proliferation and trafficking. [26][27][28][29]46 An in vivo proliferation assay demonstrated that CYM did not affect macrophage proliferation. Increasing amounts of data have indicated that the lower number of macrophages in the inflamed tissues of FTY720-treated mice could be an indirect effect of vascular permeability and monocyte recruitment.…”

Section: Discussionmentioning

confidence: 99%

The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment

Cheng

Lin

et al. 2014

Cell Mol Immunol

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FTY720, an agonist for four of the five known sphingosine-1-phosphate (S1P) receptors, has been reported to inhibit acute graft-versus-host disease (aGVHD). Because FTY720 functions through multiple S1P receptors, the mechanism of action through one or more of these receptors may account for its side effects. Thus, more selective S1P receptor modulators are needed to evaluate the roles of different S1P receptors and their therapeutic efficacies. In this study, we investigated the effect of an S1P 1 -selective agonist, CYM-5442, on the progression of aGVHD. We showed that CYM-5442 significantly inhibited but did not prevent aGVHD. CYM-5442 did not affect the infiltration of the donor T cells into the target organs, while the number of macrophages in GVHD organs was significantly reduced by CYM-5442 treatment. In vivo proliferation assays showed that the proliferation of macrophages was not suppressed by CYM-5442. Further studies using human endothelial cells demonstrated that CYM-5442 treatment downregulated CCL2 and CCL7 expression in endothelial cells, therefore reducing the migration of monocytes, from which tissue macrophages originate. Our data demonstrate the therapeutic efficacy of an S1P 1 -selective agonist in aGVHD and its possible mechanism of action. The results suggest that further investigations are needed regarding CYM-5442 as a potential therapeutic regimen for aGVHD.

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Section: Discussionmentioning

confidence: 99%

The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment

Cheng

Lin

et al. 2014

Cell Mol Immunol

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“…in transplantation and in MS. Moreover, the sphingosine kinase and S1P or its receptors are more and more identified as main Walter/Faßbender Cell Physiol Biochem 2010;26:49-56 signalling regulators in macrophages during the pathogenesis of inflammatory diseases [65].…”

Section: Spingosine and Sphingosine-1-phosphate In Msmentioning

confidence: 99%

Spingolipids in Multiple Sclerosis

Walter

Faßbender²

2010

Cell Physiol Biochem

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Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system, mainly affecting young adults. Current therapeutic approaches focus on the suppression of the immune system and on blockade of T cell blood-brain barrier transmigration into the brain parenchyma. Recently, sphingolipids that have been linked to MS pathophysiology, i.e., Sphingosine-1-phosphate (S1P), intracellularly produced lysophospholipids, can be recognized by receptors located on T and B cells. The recent demonstration that S1P is able to direct lymphocyte trafficking between blood and lymphoid system has been translated into therapeutic application: A S1P analogue, FTY720, is currently under clinical investigation in MS. Further cell membrane lipids that are involved in cell proliferation, signalling cascades and apoptosis might be of relevance in MS pathophysiology and, thus, await further investigation. This review focuses on the current knowledge on the role of sphingolipids in MS and discusses their potential therapeutical implications.

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“…Sphingolipids participate in the regulation of cell survival, proliferation, apoptosis, chemotherapeutic resistance, differentiation, endoplasmic reticulum stress response, autophagy, senescence, migration, adhesion and angiogenesis [17, [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]. Ceramide stimulates the death of a wide variety of cells including neurons [67][68][69], Tlymphocytes [70], hepatocytes [71], epithelial cells [72] and erythrocytes [30,42,44,71,73].…”

Section: Discussionmentioning

confidence: 99%

Sphingosine but not Sphingosine-1-phosphate Stimulates Suicidal Erythrocyte Death

Qadri

Bauer

Zelenak

et al. 2011

Cell Physiol Biochem

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Sphingosine kinase 1 phosphorylates sphingosine, which is converted to ceramide by ceramide synthetase. Ceramide triggers eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. Erythrocytes lack sphingosine phosphate-degrading enzymes and thus store large quantities of sphingosine phosphate. The present study explored the influence of sphingosine and sphingosine phosphate on eryptosis. [Ca²⁺]_i, was estimated from Fluo3 fluorescence, cell volume from forward scatter and PS exposure from annexin V-binding in FACS analysis. Sphingosine (0.1 – 10 µM) but not sphingosine-1- phosphate (0.1 – 10 µM) increased [Ca²⁺]_i, decreased cell volume and increased PS-exposure. The observations disclose sphingosine, but not sphingosine-1-phosphate, as a strong inducer of eryptosis.

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Regulation of macrophage function by sphingosine-1-phosphate

Cited by 97 publications

References 117 publications

The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment

The S1P1 receptor-selective agonist CYM-5442 reduces the severity of acute GVHD by inhibiting macrophage recruitment

Spingolipids in Multiple Sclerosis

Sphingosine but not Sphingosine-1-phosphate Stimulates Suicidal Erythrocyte Death

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