RESUMO
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, and PEA the phosphatidylethanolamine residue, and Flu fluorescein residue) capable of incorporation into the cell membrane were synthesized. The optimum structures of neoglycoconjugates and 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 Le(x) trisaccharide were shown to be more sensitive to the cytotoxic effect of human NK cells than the intact cells. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.
Assuntos
Membrana Celular/metabolismo , Citotoxicidade Imunológica , Glicoconjugados/metabolismo , Glicolipídeos/metabolismo , Células Matadoras Naturais/imunologia , Linhagem Celular , Membrana Celular/química , Glicoconjugados/síntese química , Glicoconjugados/química , Glicolipídeos/química , Humanos , Antígenos CD15/análise , Antígenos CD15/química , Antígenos CD15/metabolismoRESUMO
A model system was developed to study the role of cell surface oligosaccharides in cytotoxicity mediated by natural killer (NK) cells. Polymeric glycoconjugates Glyc-PAA-PE and Glyc-PAA(Flu)-PE (where Glyc is the 3-aminopropyl Le(x) residue, PAA is the poly(N-2-hydroxyethylacrylamide) matrix, Flu is the residue of a fluorescein derivative, and PE is the phosphatidylethanolamine residue) were synthesized, and their association with the membranes of living K562 cells was studied.
Assuntos
Glicolipídeos/metabolismo , Células Matadoras Naturais/metabolismo , Antígenos CD15/metabolismo , Oligossacarídeos/metabolismo , Membrana Celular/metabolismo , Testes Imunológicos de Citotoxicidade , Citometria de Fluxo , Fluoresceína/química , Glicolipídeos/química , Humanos , Oligossacarídeos/química , Fosfatidiletanolaminas/química , Células Tumorais CultivadasRESUMO
The paper proposes a mathematical model of development of a cell population with a changing proliferative activity. The model is based on the Markov branching process with cells of several types. A procedure for identifying the constructed model by experimental evidence is being developed. An example of model construction and assessment for cultured diploid fibroblasts is given.