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      Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.

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          Abstract

          Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY720. Both species were high-affinity agonists of at least four of the five S1P receptors. These agonists produce lymphopenia in blood and thoracic duct lymph by sequestration of lymphocytes in lymph nodes, but not spleen. S1P receptor agonists induced emptying of lymphoid sinuses by retention of lymphocytes on the abluminal side of sinus-lining endothelium and inhibition of egress into lymph. Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression.

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          Author and article information

          Journal
          Science
          Science (New York, N.Y.)
          American Association for the Advancement of Science (AAAS)
          1095-9203
          0036-8075
          Apr 12 2002
          : 296
          : 5566
          Affiliations
          [1 ] Department of Immunology and Rheumatology, Merck Research Laboratories, Post Office Box 2000, Rahway, NJ 07065, USA.
          Article
          1070238
          10.1126/science.1070238
          11923495
          6c09fd31-3b77-42f2-93f3-1b0b8450a3ff
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