PMID- 17339438 OWN - NLM STAT- MEDLINE DCOM- 20070522 LR - 20191210 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 178 IP - 6 DP - 2007 Mar 15 TI - Migration of CD4 T cells and dendritic cells toward sphingosine 1-phosphate (S1P) is mediated by different receptor subtypes: S1P regulates the functions of murine mature dendritic cells via S1P receptor type 3. PG - 3437-46 AB - Dendritic cells (DCs) and lymphocytes are known to show a migratory response to the phospholipid mediator, sphingosine 1-phosphate (S1P). However, it is unclear whether the same S1P receptor subtype mediates the migration of lymphocytes and DCs toward S1P. In this study, we investigated the involvement of S1P receptor subtypes in S1P-induced migration of CD4 T cells and bone marrow-derived DCs in mice. A potent S1P receptor agonist, the (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P], at 0.1 nM or higher and a selective S1P receptor type 1 (S1P(1)) agonist, SEW2871, at 0.1 muM or higher induced a dose-dependent down-regulation of S1P(1). The pretreatment with these compounds resulted in a significant inhibition of mouse CD4 T cell migration toward S1P. Thus, it is revealed that CD4 T cell migration toward S1P is highly dependent on S1P(1). Mature DCs, when compared with CD4 T cells or immature DCs, expressed a relatively higher level of S1P(3) mRNA. S1P at 10-1000 nM induced a marked migration and significantly enhanced the endocytosis of FITC-dextran in mature but not immature DCs. Pretreatment with (S)-FTY720-P at 0.1 microM or higher resulted in a significant inhibition of S1P-induced migration and endocytosis in mature DCs, whereas SEW2871 up to 100 microM did not show any clear effect. Moreover, we found that S1P-induced migration and endocytosis were at an extremely low level in mature DCs prepared from S1P(3)-knockout mice. These results indicate that S1P regulates migration and endocytosis of murine mature DCs via S1P(3) but not S1P(1). FAU - Maeda, Yasuhiro AU - Maeda Y AD - Research Laboratory III (Immunology), Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama, Japan. FAU - Matsuyuki, Hirofumi AU - Matsuyuki H FAU - Shimano, Kyoko AU - Shimano K FAU - Kataoka, Hirotoshi AU - Kataoka H FAU - Sugahara, Kunio AU - Sugahara K FAU - Chiba, Kenji AU - Chiba K LA - eng PT - Journal Article PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Immunosuppressive Agents) RN - 0 (Lysophospholipids) RN - 0 (Oxadiazoles) RN - 0 (Propylene Glycols) RN - 0 (Receptors, Lysosphingolipid) RN - 0 (S1pr3 protein, mouse) RN - 0 (SEW2871) RN - 0 (Sphingosine-1-Phosphate Receptors) RN - 0 (Thiophenes) RN - 26993-30-6 (sphingosine 1-phosphate) RN - G926EC510T (Fingolimod Hydrochloride) RN - NGZ37HRE42 (Sphingosine) SB - IM MH - Animals MH - CD4-Positive T-Lymphocytes/cytology/*immunology/metabolism MH - Cell Movement/drug effects/genetics/*immunology MH - Cells, Cultured MH - Dendritic Cells/cytology/*immunology/metabolism MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects/genetics/immunology MH - Endocytosis/drug effects/genetics/*immunology MH - Fingolimod Hydrochloride MH - Immunosuppressive Agents/pharmacology MH - Lysophospholipids/*immunology MH - Mice MH - Mice, Knockout MH - Oxadiazoles/pharmacology MH - Propylene Glycols/pharmacology MH - Receptors, Lysosphingolipid/agonists/deficiency/*immunology MH - Sphingosine/*analogs & derivatives/immunology/pharmacology MH - Sphingosine-1-Phosphate Receptors MH - Thiophenes/pharmacology EDAT- 2007/03/07 09:00 MHDA- 2007/05/23 09:00 CRDT- 2007/03/07 09:00 PHST- 2007/03/07 09:00 [pubmed] PHST- 2007/05/23 09:00 [medline] PHST- 2007/03/07 09:00 [entrez] AID - 178/6/3437 [pii] AID - 10.4049/jimmunol.178.6.3437 [doi] PST - ppublish SO - J Immunol. 2007 Mar 15;178(6):3437-46. doi: 10.4049/jimmunol.178.6.3437.