Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720.

Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Research Abstract Details 

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Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Abstract Text:

FTY720, a potent immunomodulatory drug in phase 2/3 clinical trials, induces rapid and reversible sequestration of lymphocytes into secondary lymphoid organs, thereby preventing their migration to sites of inflammation. As prerequisite for its function, phosphorylation of FTY720 to yield a potent agonist of the sphingosine-1-phosphate receptor S1P(1) is required in vivo, catalyzed by an as-yet-unknown kinase. Here, we report on the generation of sphingosine kinase 2 (SPHK2) knockout mice and demonstrate that this enzyme is essential for FTY720 phosphate formation in vivo. Consequently, administration of FTY720 does not induce lymphopenia in SPHK2-deficient mice. After direct dosage of FTY720 phosphate, lymphopenia is only transient in this strain, indicating that SPHK2 is constantly required to maintain FTY720 phosphate levels in vivo.

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Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood

VOLUME: 107

Page Numbers: 1454-8

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 13

MONTH: 10

YEAR: 2005

Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Information

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LANGUAGE: eng

NlmUniqueID: 7603509

Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Keywords Mesh Terms:

KEYWORDS: Sphingosine

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Information

Substance Name: sphingosine kinase

Registry Number: EC 2.7.1.-

Grant and Affiliation Information for Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720.

AFFILIATION: Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.

Country: United States

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MEDLINETA: Blood

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