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Literature DB >> 12618517

FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.

Shaun M Honig¹, Shuang Fu, Xia Mao, Adam Yopp, Michael D Gunn, Gwendalyn J Randolph, Jonathan S Bromberg.

Abstract

FTY720 is a sphingosine-derived immunosuppressant. Phosphorylated FTY720 promotes T cell homing from spleen and peripheral blood to LNs by acting as an agonist for sphingosine-1-phosphate (S1P) receptors. Here we demonstrate that FTY720 enhances the activity of the sphingosine transporter Abcb1 (Mdr1) and the leukotriene C(4) transporter Abcc1 (Mrp1). Both transporters must be active for FTY720-mediated T cell migration and LN homing. Migration and homing driven by FTY720, phosphorylated FTY720, or S1P also require 5-lipoxygenase-mediated synthesis of cysteinyl leukotrienes and their efflux from the cell. FTY720-mediated LN homing events further downstream are dependent on CCL19, CCL21, VLA-4alpha, and CD44. Use of T cells deficient in 5-lipoxygenase, Abcb1, and Abcc1, and comparison of the effects of FTY720 with those of S1P, suggest a model of sequential engagement of Abcb1, SP1 receptors, 5-lipoxygenase, and Abcc1 to enhance T cell migration and homing.

Entities: Chemical Gene

Mesh：

Substances：

Year: 2003 PMID： 12618517 PMCID： PMC151892 DOI： 10.1172/JCI16200

Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808

47 in total

1. A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4.

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Journal: Blood Date: 1998-04-15 Impact factor: 22.113

2. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins.

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Journal: Proc Natl Acad Sci U S A Date: 1997-04-15 Impact factor: 11.205

3. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine.

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Journal: Cell Date: 1996-11-01 Impact factor: 41.582

Review 4. Lymphocyte homing and homeostasis.

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Journal: Science Date: 1996-04-05 Impact factor: 47.728

Review 5. Pharmacologic approaches to reversing multidrug resistance.

Authors: B I Sikic
Journal: Semin Hematol Date: 1997-10 Impact factor: 3.851

6. A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo.

Authors: M Lohoff; S Prechtl; F Sommer; M Roellinghoff; E Schmitt; G Gradehandt; P Rohwer; B D Stride; S P Cole; R G Deeley
Journal: J Clin Invest Date: 1998-02-01 Impact factor: 14.808

7. Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione.

Authors: A Lorico; G Rappa; R A Finch; D Yang; R A Flavell; A C Sartorelli
Journal: Cancer Res Date: 1997-12-01 Impact factor: 12.701

8. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates.

Authors: I Leier; G Jedlitschky; U Buchholz; S P Cole; R G Deeley; D Keppler
Journal: J Biol Chem Date: 1994-11-11 Impact factor: 5.157

9. Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene.

Authors: X S Chen; J R Sheller; E N Johnson; C D Funk
Journal: Nature Date: 1994-11-10 Impact factor: 49.962

10. Diacylglycerol lipase activation and 5-lipoxygenase activation and translocation following TCR/CD3 triggering in T cells.

Authors: M G Cifone; L Cironi; A Santoni; R Testi
Journal: Eur J Immunol Date: 1995-04 Impact factor: 5.532

36 in total

Review 1. The organization and consequences of eicosanoid signaling.

Authors: Roy J Soberman; Peter Christmas
Journal: J Clin Invest Date: 2003-04 Impact factor: 14.808

2. The membrane organization of leukotriene synthesis.

Authors: Asim K Mandal; Jesse Skoch; Brian J Bacskai; Bradley T Hyman; Peter Christmas; Douglas Miller; Ting-ting D Yamin; Shihua Xu; Douglas Wisniewski; Jilly F Evans; Roy J Soberman
Journal: Proc Natl Acad Sci U S A Date: 2004-04-14 Impact factor: 11.205

10. Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells.

Authors: Lilly Y W Bourguignon; Karine Peyrollier; Weiliang Xia; Eli Gilad
Journal: J Biol Chem Date: 2008-04-25 Impact factor: 5.157

FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.

1. A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4.

2. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins.

3. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine.

Review 4. Lymphocyte homing and homeostasis.

Review 5. Pharmacologic approaches to reversing multidrug resistance.

6. A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo.

7. Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione.

8. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates.

9. Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene.

10. Diacylglycerol lipase activation and 5-lipoxygenase activation and translocation following TCR/CD3 triggering in T cells.

Review 1. The organization and consequences of eicosanoid signaling.

2. The membrane organization of leukotriene synthesis.

Review 3. Immunotherapy for De Novo renal transplantation: what's in the pipeline?

Review 4. Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient.

5. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells.

Review 6. Regulation of metabolism and transport of sphingosine-1-phosphate in mammalian cells.

7. Targeting sphingosine 1 phosphate receptor type 1 receptors in acute kidney injury.

8. Expression of 5-lipoxygenase (5-LOX) in T lymphocytes.

Review 9. Hyaluronan: a constitutive regulator of chemoresistance and malignancy in cancer cells.

10. Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells.