Publikationsdatenbank

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

Bandzählung: 71

Heftzählung: 1/2

Seiten: 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.