Activation-regulated expression and chemotactic function of sphingosine 1-phosphate receptors in mouse splenic T cells.
Sphingosine 1-phosphate (S1P) from platelets and macrophages stimulates migration and enhances survival of T cells. Mouse spleen CD4 and CD8 T cells are shown to express predominantly S1P1 (Edg-1) and S1P4 (Edg-6) G-protein-coupled receptors with only minimal representation of S1P2, S1P3, and S1P5. At and below plasma concentrations of healthy mammals (1 nM-1 microM), S1P evokes trans-Matrigel chemotaxis of mouse CD4 and CD8 T cells and recruits T cells into subcutaneous air pouches. T cell receptor-mediated activation of CD4 T cells suppresses expression of S1P1 and S1P4 receptors and eliminates their chemotactic responses to S1P. The immunoregulator FTY720, a structural homologue of S1P, lacks T cell chemotactic activity and competitively inhibits T cell chemotactic responses to S1P in vitro and in vivo. S1P may be a distinctive contributor to compartmental immunity by attracting naïve and memory T cells preferentially over activated effector T cells.
Graeler
Markus
M
Department of Medicine, University of California, San Francisco, California 94143-0711, USA.
Goetzl
Edward J
EJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D005260:Female; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D008246:Lysophospholipids; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D008246:Lysophospholipids; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine