Interleukin-2 binds to gangliosides in micelles and lipid bilayers.
Gangliosides shed from the surface of tumour cells may be involved in tumour-induced immunosuppression. These anionic sialoglycolipids are known to be potent inhibitors of lymphocyte proliferation, and it has been suggested that they interfere with processes mediated by the growth factor interleukin-2 (IL-2). We have thus investigated the interaction of IL-2 with gangliosides in micelles and lipid bilayers. Gel filtration FPLC showed that 125I-IL-2 can bind to micellar gangliosides in aqueous solution, and this interaction was strongly promoted by low concentrations of serum. Binding to ganglioside micelles was specific in that it required a native IL-2 molecule. IL-2 binding remained unchanged in the presence of 40% ethylene glycol, suggesting that it was not due to hydrophobic interactions. Ganglioside oligosaccharides alone were not able to bind to IL-2. Direct binding studies and gel filtration chromatography indicated that both multilamellar liposomes and 100 nm unilamellar vesicles containing gangliosides were able to interact with IL-2. Bilayers of lipid alone showed no binding. The interaction of IL-2 with bilayer gangliosides was highly dependent on the bilayer lipid composition, but appeared independent of lipid phase state. These results suggest that gangliosides may be a physiologically relevant target for IL-2 binding.
Chu
J W
JW
Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
Sharom
F J
FJ
D000818:Animals; D001790:Blood Physiological Phenomena; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008823:Micelles
D005732:Gangliosides; D007376:Interleukin-2; D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles