Russian Journal of Bioorganic Chemistry, Vol. 30, No. 3, 2004, š . 250
The Modification of Cell Surface with Lipophilic Glycoconjugates and the Interaction of Modified Cells with Natural Killer Cells
E. I. Kovalenko, 1 E. V. Khirova, I. M. Molotkovskaya, T. V. Ovchinnikova, M. A. Sablina, A. M. Sapozhnikov, S. V. Khaidukov, and N. V. Bovin
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow , 117997 Russia
Abstract: An experimental model system involving the modification of carbohydrate composition of the target cell surface with neoglycolipids was developed for studying the role of surface carbohydrates of target cells in the NK-cell-mediated cytotoxicity. The polymeric glycoconjugates of the Glyc–PAA–PEA and Glyc–PAA(Flu)–PEA types (where Glyc was an oligosaccharide residue, PAA poly(acrylamide) polymer, PEA the phosphatidylethanolamine residue, and Flu fluorescein residue) capable of incorporating into the cell membrane were synthesized. The optimum structures of neoglycoconjugates and the conditions for their incorporation into K562 and Raji cell lines, which differ in their sensitivity to the NK-cell-mediated lysis were selected. The mechanism of association of glycoconjugates with the plasma cell membrane and the kinetics of their elimination from the cell surface were investigated using the fluorescent-labeled Glyc–PAA(Flu)–PEA derivatives. The spatial accessibility of the carbohydrate ligands for the interaction with human NK cells was demonstrated. The target cells modified with the Lex trisaccharide were shown to be more sensitive to the cytotoxic effect of human NK cells than the intact cells.
Key words: cytotoxicity, Le x trisaccharide, neoglycoconjugates, NK cells