The alliance of sphingosine-1-phosphate and its receptors in immunity

Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland 20892, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 10/2008; 8(10):753-63. DOI: 10.1038/nri2400
Source: PubMed


Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune-cell trafficking. Its concentration is increased in many inflammatory conditions, such as asthma and autoimmunity. Much of the immune function of S1P results from the engagement of a family of G-protein-coupled receptors (S1PR1-S1PR5). Recent findings on the role of S1P in immunosurveillance, the discovery of regulatory mechanisms in S1P-mediated immune-cell trafficking and new advances in understanding the mechanism by which S1P affects immune-cell function indicate that the alliance between S1P and its receptors has a fundamental role in immunity.

Download full-text


Available from: Richard L Proia, Jul 18, 2014
    • "However these effects make S1P as an essential factor for physiological development of organs such as brain and heart, as well as maturation of the systemic circulatory and lymphatic system , but these effects could also make S1P as an oncogenic lipid that promotes tumor growth and progression[8,22]. In addition to the mentioned functions, S1P also play an important role in the regulation of endothelial barrier function of the vascular system[23], as well as modulation of the immune system[24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sphingosine-1 phosphate (S1P), a bioactive sphingolipid metabolite, plays an essential role in cellular homeostasis. It is well evidenced that enzymes responsible for S1P production, as well as S1P receptors are expressed in the central nervous system (CNS), implying that S1P may contribute to CNS physiology. In current review, we will present the current knowledge about developmental and neuromodulatory functions of S1P in the brain. Considering neuroprotective effects of S1P, we also review the relation between S1P and cellular autophagy, mitochondrial function, oxidative stress and apoptosis as well as molecular pathways underlying neuroprotective effects of S1P. Given these pivotal functions, in the last section, we will summarize latest findings about possible contribution of S1P dysregulation in neurological disorders like Alzheimer's disease and Multiple sclerosis.
    No preview · Article · Jan 2016 · Pharmacological Research
  • Source
    • "S1PR1 is expressed by the majority of innate and adaptive immune cells such as macrophages, eosinophils, dendritic cells, mast cells, natural killer cells, T cells, B cells, and natural killer T cells (Dorsam et al., 2003; Jolly et al., 2004; Roviezzo et al., 2004; Czeloth et al., 2007; Allende et al., 2007; Hughes et al., 2008; Rivera et al., 2008). The other receptors from this family (S1PR2, S1PR3, S1PR4, and S1PR5) are expressed in only a few cell types of the immune system with an overlapping but distinct pattern of expression according to the tissue (Sanchez and Hla, 2004; Rivera et al., 2008). The river buffalo (Bubalus bubalis) plays an important role in the worldwide economy through the production of high-quality milk and meat. "

    Full-text · Article · Jan 2016 · Genetics and molecular research: GMR
  • Source
    • "In other cell types, that is, breast cancer and mast cell, the ABC (ATP-binding cassette) transporter family members ABCC1 and ABCG2, known regulators of inflammatory processes, facilitate export of S1P across the cell membrane [35, 36]. S1P regulates a diverse range of cellular processes that are important in immunity, inflammation , and inflammatory disorders [37, 38]. Once secreted, most of the S1P binds to albumin or serum lipoproteins [39]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sphingosine-1-phosphate (S1P) is a versatile lipid signaling molecule and key regulator in vascular inflammation. S1P is secreted by platelets, monocytes, and vascular endothelial and smooth muscle cells. It binds specifically to a family of G-protein-coupled receptors, S1P receptors 1 to 5, resulting in downstream signaling and numerous cellular effects. S1P modulates cell proliferation and migration, and mediates proinflammatory responses and apoptosis. In the vascular barrier, S1P regulates permeability and endothelial reactions and recruitment of monocytes and may modulate atherosclerosis. Only recently has S1P emerged as a critical mediator which directly links the coagulation factor system to vascular inflammation. The multifunctional proteases thrombin and FXa regulate local S1P availability and interact with S1P signaling at multiple levels in various vascular cell types. Differential expression patterns and intracellular signaling pathways of each receptor enable S1P to exert its widespread functions. Although a vast amount of information is available about the functions of S1P and its receptors in the regulation of physiological and pathophysiological conditions, S1P-mediated mechanisms in the vasculature remain to be elucidated. This review summarizes recent findings regarding the role of S1P and its receptors in vascular wall and blood cells, which link the coagulation system to inflammatory responses in the vasculature.
    Full-text · Article · Oct 2015 · Mediators of Inflammation
Show more