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E V Sinitsyna

Publications and source records attributed to E V Sinitsyna.

13 recordsLinked to original sources

The role of glycosphingolipids in natural immunity. Gangliosides modulate the cytotoxicity of natural killer cells.

Incubation of gangliosides with natural killer (NK) cells from various sources was found to inhibit NK activity in vitro whereas incubation of the same gangliosides with human or mouse lymphoma cells prior to their exposure to NK effectors resulted in a sharp increase in the NK sensitivity of the tumor cells. These effects depended on the oligosaccharide structure of the gangliosides and on the origin of the NK effector cells. The lysis of YAC cells by mouse splenocytes or of MOLT-4 cells by NK cells isolated from the peripheral blood of Syrian hamsters or humans was inhibited most strongly by pre-incubation of the effector cells with gangliosides GM3 and GD3 which are known to be elevated in the serum of tumor-bearing hosts. It is suggested that target cell-associated gangliosides may function as target structures recognized by NK cells while serum gangliosides may contribute to the inhibition of NK cells during tumor development and thus help the tumor to escape NK surveillance.

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[Effect of gangliosides on the cytotoxic activity of natural killers from Syrian hamsters].

The ability of various gangliosides to inhibit the cytotoxic activity of natural killers (NK-cells) from Syrian hamsters towards human lymphoma MOLT-4 cells was studied. The inhibitory effect was found to depend on the structure and concentration of the gangliosides. At concentrations corresponding to those in the blood of tumour-bearing hosts, SiaLacCer and Sia2LacCer inhibited the NK-activity. A significant inhibition was also found for (NeuAc)2GgOse3Cer, whereas NeuGcGgOse3Cer and NeuAcGgOse4Cer were practically inactive. Previously it was shown that Sia2LacCer which is either absent or very low in normal blood, is produced by a number of tumours and that tumour cells "shed" considerable amounts of gangliosides. On this ground, it was proposed that elevated concentrations of SiaLacCer and Sia2LacCer in the blood of tumour-bearing animals may inhibit the NK-activity and thus contribute to the "escape" of tumour cells from host immune surveillance.

Animals↗

[Effect of glycosphingolipids on the activity of natural killer cells].

The effects of exogenous glycosphingolipids on the cytotoxic activity of natural killer (NK) cells and on the sensitivity of target cells were studied. Incubation of splenocytes with gangliosides of the hemato-series (GM3 and GD3) or with their precursor, LacCer, decreases the cytotoxic NK-activity, whereas some other acidic and neutral glycolipids do not possess such capability. On the other hand, incubation of target (YAC lymphoma) cells with glycolipids of the hemato-series increases the sensitivity of these cells to the cytotoxic action of NK-cells. A comparison of the ganglioside profiles of two YAC call lines differing in their NK-sensitivity revealed the presence of a GD3-like component in the highly sensitive cell line and the absence of this ganglioside in low sensitive target cells. It is assumed that gangliosides of the hemato-series are components of the acceptor complex on the surface of the target cells and that shedding of these gangliosides (especially, of GD3) by tumour cells is one possible mechanism of NK-activity suppression during malignant growth.

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Shedding of gangliosides from calf thymocytes.

In the course of our work on calf thymus gangliosides [Dyatlovitskaya, Zablotskaya, Azizov & Bergelson (1980) Eur. J. Biochem. 110, 475-483] we studied the gangliosides exfoliated from the cell surface of thymocytes. It was shown that calf thymocytes shed gangliosides both in vivo and in vitro. Various gangliosides were found to be present in high amounts both in extracellular plasma membrane vesicles and in the 64000 X g supernatant. The extracellular membrane fragments were comparatively higher in disialosyllactosylceramide and the 64000 X g supernatant was higher in sialosyllactosylceramide than the cells. Comparison of the ganglioside composition of extracellular membrane fragments, thymocytes and lymphocytes led us to suggest that the shedding of gangliosides from the surface of thymocytes may be involved in the transformation of immunologically incompetent cortical thymocytes into immunocompetent virgin T-cells.

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[Dependence of ganglioside composition of leukemic lymphocytes on density cell population density].

A comparative study of gangliosides from bovine normal lymph lymphocytes and leukemic blood lymphocytes and from calf thymocytes incubated at different cell densities was carried out. The ganglioside composition of thymocytes and normal lymphocytes was insensitive to the variations in cell density. In the case of leukemic lymphocytes the decrease of cell density resulted in a reduction of the absolute and relative content of one of the major ganglioside components, disialosyllactosylceramide, and in a concomitant increase of its precursor, N-glycoloylneuraminosyllactosylceramide. The content of the third major ganglioside component, sialosylparagloboside, did not depend on cell density. The cell density dependent changes in the ganglioside composition of leukemic lymphocytes are qualitatively coincident with those observed at variable concentrations of blood lymphocytes in leukemic animals. A possible mechanism underlying the differences in ganglioside metabolism during cell density changes in leukemic lymphocytes is discussed.

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[Gangliosides of pig and human thymuses].

The ganglioside composition of thymuses from pigs of different age, of embryonal human thymus and of thymus from newborns was studied. Pig thymus was found to contain 8 ganglioside fractions, i. e. N-acetyl- and N-glycoloylneuraminosyllactosylceramides (GM3), N-acetyl- and N-glycoloylneuraminosylgangliotetraosylceramides (GM1), (N-acetylneuraminosyl, N-glycoloylneuraminosyl)- and di(N-glycoloylneuraminosyl)lactosylceramides (GD3), N-glycoloylneuraminosylgangliotriaosylceramide (GM2) and a fucoganglioside. The ganglioside spectrum of pig thymus did not change with ageing. In embryonal human thymus and in thymus of newborns four ganglioside fractions were determined, i.e. GM3, N-acetylneuraminosylneolactotetraosylceramide GM2 and GD3. A comparison of the experimental results with literature data suggests that ganglioside GD3 is a marker of immature lymphoid cells displaying a marked phylogenetic stability.

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[Immunological detection of sphingomyelin exchange protein in tumors and in embryonic rat liver].

The interaction of postmicrosomal supernatants from the Jensen sarcoma, sarcoma 45, nephroma RA, normal, regeherating and fetal rat livers with antisera to the sphingomyelin exchange protein isolated from hepatoma 27 was studied by double immunodiffusion. It was shown that this protein is present in comparable amounts in all the tumours tested and in fetal rat liver, whereas in normal and regenerating liver its content is negligible. Based on the correlation between the content of sphingomyelin exchange protein in cell cytosols and the amount of sphingomyelin in the corresponding mitochondria it is suggested that this protein is responsible for the presence of sphingomyelin in mitochondria.

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[New method of lysophospholipid incorporation into biological membranes. Effect of lysophosphatidylcholine on the activity of membrane-bound enzymes].

The incorporation of lysophosphatidylcholine into biological membranes and its effect on some membrane-bound enzymes of mitochondria and microsomes from rat liver and hepatoma were studied. It was shown that in the presence of lipid-exchange proteins of the liver a far greater amount of lysophosphatidylcholine is incorporated into the membranes than in the-iv absence. The increase of the lysophosphatidylcholine content in the membranes has no effect on the activity of mitochondrial monoamine oxidase, inhibits the activity of microsomal cytochrome P-450 and activates glucose-6-phosphatase.

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[Use of lipid exchange proteins for investigation of lipid dependence of rat liver cytochrome P-450].

The ability of lipid exchange proteins to introduce foreign phospholipids into intact microsomes was used for a study of the lipid dependence of rat liver cytochrome P-450. Cytochrome P-450 was converted into inactive cytochrome P-420 by treatment of rat liver microsomes with lysophosphatidylcholine. When such microsomes were incubated with phosphatidylcholine in the presence of lipid exchange proteins the lysophosphatidylcholine was partly replaced by phosphatidylcholine and the inactive cytochrome P-450 was reactivated. Similar incubation of the inactivated microsomes with phosphatidylethanolamine did not lead to reactivation of the enzyme.

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[Inhibition of the cytotoxic activity of natural killer cells by glycosphingolipids. Effect of the structure of carbohydrate chains].

The ability of various glycosphingolipids to inhibit the cytotoxic activity of natural killer (NK) cells was studied. The inhibitory effect was found to depend on the structure and concentration of the glycosphingolipids. Gangliosides SiaLacCer inhibited the NK activity most effectively and their inhibitory effect depended on the structure of sialic acids: the N-acetyl form was more active than the N-glycoloyl form. Elongation of the carbohydrate chain decreased the inhibitory effect and monosialogangliosides NeuGcGgOse3Cer and NeuAcGgOse4Cer were practically inactive. The inhibitory ability of disialogangliosides depended on the structure of the carbohydrate chain as well as on the structure and attachment site of the sialic acids. Previously it was found that ganglioside (NeuAc)2LacCer, which is absent or very low in normal blood, is produced by a number of tumors and alongside with NeuAcLacCer is present in elevated amounts in the blood of tumor-bearing subjects. Elevated concentration of these gangliosides in the blood of tumor hosts may inhibit apparently the NK activity and thus contribute to the escape of tumor cells from host immune surveillance.

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