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Biomedical subjects

L D Bergelson

Publications and source records attributed to L D Bergelson.

At least 19 recordsLinked to original sources
PubMed1995

Serum gangliosides as endogenous immunomodulators.

Gangliosides suppress various immune activities in vitro and in vivo. Their level is significantly elevated in tumors and atherosclerotic aorta tissue, as well as in the sera of patients with tumors or atherosclerosis. Here, Lev Bergelson suggests that ganglioside-induced immunomodulation might be involved in atherogenesis and carcinogenesis, and describes a hypothesis that cites gangliosides as a factor interfering with the clearance of low-density lipoproteins (LDLs) and promoting the formation of atherosclerotic plaques.

Animals↗
PubMed1991

Interaction of low-density lipoproteins with gangliosides.

The ganglioside uptake capacity of human serum low-density lipoproteins (LDL), the mode of ganglioside-LDL binding, and the influence of gangliosides on the floatation properties, size distribution, stability and fluorescence of LDL were investigated. The data obtained suggest that both hydrophobic and electrostatic forces are involved in formation of ganglioside-LDL complexes, but the former appear to be more important. Although association of gangliosides with LDL is predominantly unspecific, nonsaturable, and weak, a small saturable component due to specific ganglioside-apolipoprotein binding, also appears to be involved. In the presence of gangliosides the lipoprotein particles aggregate, the intrinsic fluorescence of LDL and their interaction with antibodies against apo-B change indicating that the state of apo-B [corrected] is modified by gangliosides.

Antigen-Antibody Reactions↗
PubMed1991

Low-density lipoproteins interact with liposome-binding sites on the cell surface.

Under physiological conditions significant amounts of low-density lipoprotein LDL particles ar taken up by cells independently of specific high-affinity LDL receptors (apo-B receptors). Previously it was established that some cells contain surface sites capable of binding liposomes. We proposed that liposome-binding sites could contribute to LDL interaction with the cell surface via phospholipid molecules of LDL particles. To check this hypothesis we studied the competitive interaction of human LDL and DPPC liposomes with mouse embryo fibroblasts depleted of apo-B receptors by preliminary incubation with LDL. We have found that after removal of the liposome-binding sites from cell lamellae these areas of the cell surface lose their ability to bind LDL.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

Influence of ganglioside GM3 and its breakdown products on lymphoblastic transformation and T-suppressor activity.

The influence of ganglioside GM3 and some of its breakdown products on phytohemagglutinin-induced blast transformation of human lymphocytes and concanavalin-A-induced T-suppressor activity was studied. The structures of two major hydrolysis products of GM3 were established by negative-ion fast-atom-bombardment mass spectrometry as neuraminyllactosylsphingosine (NeuLacSph) and neuraminyllactosylceramide (NeuLacCer). Both substances were shown to be potent inhibitors of mitogen-induced lymphoblastic transformation whereas their acetylation products NeuAcLacSphAc and GM3 did not affect the proliferative response of lymphocytes to phytohemagglutinin. On the other hand, only GM3 and NeuLacSph were able to enhance concanavalin-A-induced T-suppressor activity. On the basis of these data, it is suggested that the effects of GM3 and its breakdown products on lymphoblastic transformation and T-suppressor activity must rest on different mechanisms and that N-deacylation of GM3 appears to be an essential step in conversion of the ganglioside into an inhibitor of lymphocyte blast transformation.

Carbohydrate Sequence↗
PubMed1991

Ganglioside GM3 stimulates the uptake and processing of low density lipoproteins by macrophages.

Preincubation of low density lipoproteins (LDL) with low concentrations of the ganglioside GM3 (1-2x 10(-5) M/2.5 x 10(-6) M LDL-protein) results in an increase of LDL-uptake, enhances cholesterol accumulation and cholesteryl ester formation by macrophages. At the same time the lysosomal degradation of LDL in macrophages was inhibited under these conditions. These effects depended on the ganglioside structure and concentration. It is suggested that the effects observed could be caused by GM3-induced modification of LDL to a form that becomes recognized by macrophages.

Animals↗
PubMed1990

Effect of gangliosides on binding, internalization and cytotoxic activity of ricin.

The only gangliosides in Burkitt's lymphoma EB-3 cells is GM3. Treatment of Burkitt's lymphoma EB-3 cells with gangliosides GM1 or GM3 results in their binding to and partial incorporation into the cell membrane. About 25% of cell-associated ganglioside GM1 can interact with the ricin. However, such an increase in the number of binding sites does not enhance but rather decreases the cytotoxic effect of ricin. A similar protective effect was observed when the cells were pretreated with ganglioside GM3. In contrast, the increase in ricin biding sites caused by pretreatment of the cells with neuraminidase was accompanied by increase in ricin cytotoxicity. These differences may be related to observed differences in the rate of ricin-endocytosis by native and ganglioside-treated cells.

Binding Sites↗
PubMed1990

The interaction of prostaglandin E1 with serum lipoproteins. Possible role in cholesterol homeostasis.

Prostaglandin (PG) E1 significantly stimulates the rate of cholesterol esterification in plasma. This effect could be attributed to an enhancement by PGE1 of the interlipoprotein transfer of phosphatidylcholine and cholesteryl esters, i.e., the substrate and product of lecithin-cholesterol acyltransferase (LCAT). The enhancement effect appears to be due to a rearrangement of the lipoprotein surface induced by specific interaction of PGE1 with some apolipoproteins, although the binding capacity of serum lipoproteins for PGE1 was found to be rather weak. To explain these findings, an hypothetical non-equilibrium model was put forward. The purpose of the present article is to summarize available data on the PGE1-lipoprotein interaction.

Alprostadil↗
PubMed1990

Immunomodulatory effects of human placenta gangliosides.

The immunomodulatory properties of the major gangliosides of human placenta were studied. All the gangliosides investigated suppressed the cytotoxic activity of human natural killer cells. The magnitude of the inhibitory effect depended on ganglioside structure. Gangliosides GM1, GM3, and GD3 were the most effective suppressors. Some of the placental gangliosides (GD3, GD1a, IV3NeuAc-nLc4Cer, VI3NeuAc-nLc6Cer) also inhibited lymphoblastic transformation, and one of them (GM3) strongly stimulated the Con-A-induced T-suppressor activity of human lymphocytes. It is suggested that the combined action of the placental gangliosides on maternal effector cells may be involved in the defence of the human embryo against the maternal immune system.

Cytotoxicity, Immunologic↗
PubMed1989

Gangliosides of sea urchin embryos. Their localization and participation in early development.

The influence of antibodies to gangliosides of sea urchin Strongylocentrotus intermedius eggs on early embryos of this species was studied. gamma-Globulins were isolated from rabbit anti-ganglioside serum by micropreparative electrophoresis. These gamma-globulins produced anomalies in the development of embryos permeabilized in Triton X-100. The anomalies were not observed when anti-ganglioside gamma-globulins were added to the incubation medium together with gangliosides or when the permeabilized embryos were incubated with gamma-globulins of normal rabbit serum. Pretreatment of S. intermedius embryos with serotonin, tryptamine or some other indole derivatives led to the disappearance of ganglioside determinants from the cell surface and sharply increased immunofluorescence within the cell. Such pretreatment of embryos increased the amount of cell-associated gangliosides more than threefold as compared to untreated embryos. Serotonin was shown to bind specifically to sea urchin gangliosides immobilized on octyl-Sepharose. These observations suggest that cell-surface gangliosides, after binding drugs, are internalized and that serotonin and its antagonists inhibit the transport of newly synthesized gangliosides to the cell-surface membrane.

Animals↗
PubMed1989

Use of lipophilic fluorescent probes for the isolation of hybrid cells in flow cytometry.

Flow cytometry was used for the isolation of hybrid cells immediately after fusion. Precursor cells were stained by two lipophilic fluorescent probes: perylenoyl-labeled triglyceride (perylenoyl-TG, green fluorescence, 520 nm) and rhomdaminyl-labeled triglyceride (rhodaminyl-TG, red fluorescence, greater than 580 nm). Since the maximum emission of perylenoyl-TG coincides with the maximum absorbance of rhodaminyl-TG, the two fluorescent dyes form an effective donor-acceptor pair. Cells stained by perylenoyl-TG (0.25-1 microgram/ml) at the excitation wavelength of 457 nm displayed high intensity of fluorescence in the green region (520 nm), and low intensity of fluorescence in the red region (greater than 580 nm). Using the same conditions, cells that were stained by rhodaminyl-TG displayed a low intensity of fluorescence in both regions. When cells were simultaneously labeled by perylenoyl-TG and rhodaminyl-TG (used in a concentration ratio of 1:10, respectively) essentially total energy transfer was observed, and the cells exhibited a high intensity of red fluorescence. After the fusion of cells which had been separated stained by perylenoyl-TG and rhodaminyl-TG, the hybrid cells containing the two fluorescent probes had a high intensity of red fluorescence. Resonance exitation energy transfer between the two fluorescent dyes permits effective sorting of hybrid cells by flow cytofluorometry.

Cell Fusion↗
PubMed1989

Neutral glycolipids of atherosclerotic plaques and unaffected human aorta tissue.

The composition, structure and localization of neutral glycosphingolipids of human aorta taken from subjects who had died after myocardial infarction were studied. Individual glycosphingolipids were purified by high-performance liquid chromatography and were characterized on the basis of their chromatographic mobility, carbohydrate composition, methylation analysis and by 1H-NMR spectroscopy. The main aortic glycosphingolipids were identified as glucosylceramide, lactosylceramide, globotriaosylceramide and globotetraosylceramide. Significant differences in the neutral glycosphingolipid composition of intima and media were detected. The neutral glycosphingolipid profile of medial plaques resembled that of unaffected media; however, significant differences were detected between intimal plaques and unaffected intima. Whereas the latter contained trihexosylceramide and globoside as the only neutral glycolipids, the intimal plaque glycolipids consisted mainly of glucosylceramide and also contained appreciable amounts of lactosylceramide which were completely absent in the unaffected intima. In comparison to intimal plaques, unaffected intima is characterized by a much higher content of cerebrosides terminating by beta-galactosyl residues which are known to interact with growth factors and other external stimuli. It thus seems possible that the proliferative activity of smooth muscle cells in atherosclerotic diseases is to some extent associated with their neutral glycolipid profile.

Adult↗
PubMed1989

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.

Animals↗
PubMed1989

The interaction of prostaglandins with human serum lipoproteins.

Using high density and low density lipoproteins (HDL and LDL) labeled with fluorescent analogues of phosphatidylcholine or sphingomyelin it was found that low amounts (10(-12) M) of prostaglandins E1 and F2 alpha induced different structural rearrangements of the lipoprotein surface, whereas prostaglandins E2 and F1 alpha had no effect. The effects of prostaglandin E1 on HDL were largely paralleled by those of this prostaglandin on synthetic recombinants prepared from pure apolipoprotein A1, phospholipids and cholesterol and were demonstrated to be caused by prostaglandin-apolipoprotein interaction. The interaction resembled that of a ligand with a specific receptor protein because it was specific, reversible, concentration and temperature dependent and saturable. However the retaining capacity of HDL or LDL for prostaglandin E1 as determined by equilibrium dialysis was very low and a single prostaglandin E1 molecule was able to induce structural changes in large numbers of discrete lipoprotein particles. To explain this remarkable fact a non-equilibrium model of ligand-receptor interaction is proposed. According to that model in open systems characterized by weak ligand-receptor binding, high diffusion rate of the ligand and long relaxation times which exceed the interval between two successive receptor occupations, the ligand-induced changes will accumulate, resulting in transformation of the system into a new state which may be far away from equilibrium. It is emphasized that the low mobility of lipids constituting the environment of the receptor protein plays a critical role in this type of signal amplification. It was further demonstrated that the PGE1-induced changes of the lipoprotein surface resulted in an enhancement of LDL-to-HDL transfer of cholesterol esters and phosphatidylcholine especially in the presence of serum lipid transfer proteins. The acceleration of the interlipoprotein transfer caused by prostaglandin E1 in turn increases the rate of cholesterol esterification in serum. It is suggested that in such a way prostaglandin E1 may influence the homeostasis of cholesterol.

Binding Sites↗
PubMed1989

Ganglioside content and composition of cells from normal and atherosclerotic human aorta.

The ganglioside content and composition of cells obtained by enzyme digestion of 2 layers of human aortic intima were investigated. Five gangliosides were identified in cells isolated from the external musculo-elastic intimal layer adjacent to the media: GM3, GM1, GD3, GD1a, and GT1b. The same gangliosides plus ganglioside Gx, the chromatographic mobility of which corresponded to the mobility of ganglioside GD1b from human brain, were found in cells from the internal elastic-hyperplastic intimal layer adjacent to the vessel lumen. In both layers, the major cellular ganglioside was GM3 which represented 60% of the total cellular ganglioside content. The ganglioside content was lower in cells obtained from fatty streaks compared to cells isolated from unaffected intima. The amount of di- and trisialogangliosides in atherosclerotic plaque cells was lower, and that of monosialogangliosides higher than in cells isolated from unaffected intima. The amount of GM3 was mainly responsible for the difference in the total ganglioside content of cells obtained from different lesion types. On the whole, cells from fatty streaks contained smaller amounts of total gangliosides, whereas cells from plaques had greater total ganglioside content, than cells from unaffected intima.

Adult↗
PubMed1989

Gangliosides influence experimental influenza virus infection in mice.

Influenza virus infection in mice may be either stimulated or partially prevented by certain gangliosides, depending on the experimental conditions employed. When injected prior to virus infection gangliosides increased the mortality rate, whereas preincubation with the virus before infection had a protecting effect. Hybrid mice resistant to influenza virus became highly susceptible to infection after injection of a specific ganglioside whereas the corresponding antiganglioside antiserum protected virus-susceptible mice against infection by the virus. These results are discussed in the light of earlier findings that various gangliosides enhance non-specific binding of influenza virus, whereas gangliosides of the GT1b and GD1b type are able to act as specific virus receptors and to promote virus penetration.

Animals↗
PubMed1988

The interaction of prostaglandins with serum low-density lipoproteins.

The interaction of human serum low-density lipoproteins (LDL) with various types of prostaglandins (PG) was studied using equilibrium dialysis, steady-state fluorescence polarization spectroscopy and photolabeling methods. Low concentrations (10(-13)-10(-9) M) of PGE1 and PGF2 alpha were shown to induce specific rearrangements of the lipids on the LDL surface, whereas the closely related PGE2 and PGF1 alpha had no effect. With fluorescent labeled LDL, the PGE1-induced changes of the steady-state fluorescence polarization (P) were shown to be time- and concentration-dependent, saturable and reversible. However, equilibrium dialysis revealed a very low binding capacity of LDL for PGE1 (approx. 1 prostaglandin molecule per 600 LDL particles). Approximately the same PGE1 concentration was sufficient to cause maximal changes of P, to enhance the binding to apolipoprotein B of a photoreactive sphingomyelin analogue inserted into the LDL surface and to alter the thermal phase behavior of the LDL surface lipids. It is proposed that the LDL surface rearrangement caused by prostaglandins is due to the interaction of prostaglandins with apolipoprotein B, resulting in formation of short-lived complexes. The mechanism of this interaction is discussed in terms of the non-equilibrium ligand-receptor interaction model proposed earlier to explain the interaction of prostaglandins with high-density lipoproteins (Bergelson, L.D. et al. (1987) Biochim. Biophys. Acta 921, 182-190). It is suggested that direct prostaglandin-lipoprotein interactions may play a role in the homeostasis of cholesterol.

Alprostadil↗
PubMed1988

A new approach to studies of cell-antibody interactions using fluorescent lipid probes.

The interaction of poly- and monoclonal antibodies against the L-chain of human Ig with Burkitt lymphoma EB-3 cells was studied using a fluorescent lipid probe, anthrylvinyl-labelled sphingomyelin, incorporated into the cell plasma membrane. Binding of the antibodies to Ig receptors on the surface was shown to induce changes in the fluorescence polarization of the probe. The high sensitivity of the method allows one to detect less than 100 antibody molecules per cell. The possibility of using cells or liposomes carrying antigens and fluorescent lipids for the determination of antibodies in solution is discussed.

Antibodies, Anti-Idiotypic↗