Novel mediators of FTY720 in human lymphocytes.
FTY720 (FTY), a novel immunosuppressive drug, can be distinguished from other immunosuppressive drugs by a completely different mechanism of action. FTY induces altered lymphocyte trafficking, leading to peripheral blood lymphopenia and to increased lymphocyte counts in lymph nodes. FTY mediates its immune-modulating effects by binding to sphingosine 1-phosphate receptors expressed on lymphocytes. In an attempt to identify mediators of the FTY-induced signal transduction, we used a proteomic approach. FTY-treated peripheral blood lymphocytes (PBLs) were investigated for the expression of 622 proteins. We identified 15 differentially expressed proteins in PBLs possibly related to FTY action. As indicated by protein function, several identified proteins could be linked to the cytoskeleton/cell motility, to cell adhesion, and vesicle trafficking. No changes were found concerning the expression of various apoptosis regulators as well as the immunophilins FKBP12 and calcineurin. Our data suggest that FTY affects cytoskeleton rearrangements, cell adhesion, and vesicle trafficking/sorting in human PBLs.
Böhler
Torsten
T
Department of Internal Medicine-Nephrology, Charité Campus Mitte, Humboldt-University Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany. torsten.boehler@charite.de
Budde
Klemens
K
Neumayer
Hans-H
HH
Waiser
Johannes
J
D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011409:Propylene Glycols / Q000494:pharmacology*; D040901:Proteomics; D013110:Sphingosine / Q000031:analogs & derivatives; D044763:Ubiquitin-Conjugating Enzymes / Q000032:analysis; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D044763:Ubiquitin-Conjugating Enzymes; D019869:Phosphatidylinositol 3-Kinases; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine