Scholars@Duke publication: FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.

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

Publication , Journal Article

Honig, SM; Fu, S; Mao, X; Yopp, A; Gunn, MD; Randolph, GJ; Bromberg, JS

Published in: J Clin Invest

March 2003

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.

Duke Scholars

Author Michael Dee Gunn Medicine, Cardiology

Published In

J Clin Invest

DOI

10.1172/JCI16200

ISSN

0021-9738

Publication Date

March 2003

Volume

111

Issue

Start / End Page

627 / 637

Location

United States

Related Subject Headings

T-Lymphocytes
Sphingosine
Receptors, Lysophospholipid
Receptors, G-Protein-Coupled
Receptors, Cell Surface
Propylene Glycols
Phosphorylation
Multidrug Resistance-Associated Proteins
Mice, Inbred C57BL
Mice

Citation

APA

Chicago

ICMJE

MLA

NLM

Honig, S. M., Fu, S., Mao, X., Yopp, A., Gunn, M. D., Randolph, G. J., & Bromberg, J. S. (2003). FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest, 111(5), 627–637. https://doi.org/10.1172/JCI16200

Honig, Shaun M., Shuang Fu, Xia Mao, Adam Yopp, Michael D. Gunn, Gwendalyn J. Randolph, and Jonathan S. Bromberg. “FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.” J Clin Invest 111, no. 5 (March 2003): 627–37. https://doi.org/10.1172/JCI16200.

Honig SM, Fu S, Mao X, Yopp A, Gunn MD, Randolph GJ, et al. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest. 2003 Mar;111(5):627–37.

Honig, Shaun M., et al. “FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.” J Clin Invest, vol. 111, no. 5, Mar. 2003, pp. 627–37. Pubmed, doi:10.1172/JCI16200.

Honig SM, Fu S, Mao X, Yopp A, Gunn MD, Randolph GJ, Bromberg JS. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest. 2003 Mar;111(5):627–637.