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    Inhibition of sphingolipid synthesis impairs cellular activation, cytokine production and proliferation in human lymphocytes (2005)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Blank, Norbert
    Schiller, Martin
    Gabler, Christoph
    Kalden, Joachim R
    Lorenz, Hanns-Martin
    Quelle
    Biochemical pharmacology; 71(1/2) — S. 126–135
    ISSN: 0006-2952
    Sprache
    Englisch
    Verweise
    Pubmed: 16263092
    Kontakt
    Institut für Veterinär-Biochemie

    Oertzenweg 19 b
    14163 Berlin
    +49 30 838 62225
    biochemie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    The localisation of the T cell receptor and other signalling molecules in membrane microdomains (MM) is essential for the activation of T lymphocytes. These MM are stabilized by sphingolipids and cholesterol. It was recently shown that the activation of T lymphocytes leads to the confluence of small MM and the formation of an immunological synapse which is thought to be essential for a persistent activation and proliferation. We studied the effects of an inhibition of sphingolipid synthesis on T lymphocyte function. Both sphingolipid inhibitors, PDMP and myriocin, inhibited glucosphingolipids in whole cell lipid extracts and in MM. Both compounds inhibited the proliferation of superantigen-stimulated PBMC without inducing cell death. However, only the ceramide-like compound PDMP inhibited the expression of activation markers and the secretion of IFN-gamma which was not seen with myriocin treatment. The MM localisation of Lck and LAT was not significantly reduced in PDMP-treated cells. In conclusion, our results show that glucosphingolipids are necessary for cell growth of human T lymphocytes. However, inhibition of glucosphingolipid synthesis itself did not inhibit cellular activation. Our data show that glucosphingolipids - in contrast to cholesterol - are not essential for the stabilisation of MM.