Effect of micellar and bilayer gangliosides on proliferation of interleukin-2-dependent lymphocytes.
Micellar gangliosides are potent inhibitors of the proliferation of the murine interleukin-2-dependent cell lines HT-2 and CTLL-2 in vitro. The glycolipids abolished both DNA and protein synthesis, and depressed cellular expansion, without affecting viability. These effects were reversible for at least 12 hr following ganglioside treatment. Highly sialylated gangliosides were more inhibitory, while structurally related molecules, including ganglioside oligosaccharides, simple and complex neutral glycosphingolipids, sulfatides, sphingomyelin, ceramides, and sphingosine had only small suppressive effects. Gangliosides were most effective as inhibitors when added during the first 4 hr of culture with the growth factor. Inhibition of DNA synthesis by gangliosides could be partially reversed by high concentrations of exogenous interleukin-2. Gangliosides incorporated into lipid bilayers, both multilamellar liposomes and unilamellar vesicles, were also effective inhibitors of interleukin-2-induced proliferation. Competition studies showed that both ganglioside micelles and lipid vesicles containing gangliosides prevented binding of 125I-interleukin-2 to high-affinity receptors on the lymphocyte surface. We have recently shown that gangliosides, in both micelles and lipid bilayer vesicles, are able to bind interleukin-2 (J. W. K. Chu and F. J. Sharom, Biochim, Biophys. Acta 1028, 205, 1990). Taken together, these results strongly suggest that inhibition of lymphocyte proliferation by gangliosides in micelles and vesicles arises as a direct result of competition between the glycolipids and high-affinity receptors for available interleukin-2.
Chu
J W
JW
Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
Sharom
F J
FJ
D004247:DNA / Q000096:biosynthesis; D005732:Gangliosides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008051:Lipid Bilayers; D008213:Lymphocyte Activation / Q000187:drug effects*; D008823:Micelles; D014176:Protein Biosynthesis; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000494:pharmacology
D005732:Gangliosides; D007376:Interleukin-2; D008051:Lipid Bilayers; D008823:Micelles; D015375:Receptors, Interleukin-2; D014168:Transferrin; D015847:Interleukin-4; D004247:DNA