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Biomedical subjects

L D Bergelson

Publications and source records attributed to L D Bergelson.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1988

Binding of specific ligands to muscarinic receptors alters the fluidity of membrane fragments from rat brain. A fluorescence polarization study with lipid-specific probes.

The previously suggested method of following ligand-receptor interactions by measuring ligand-induced changes in membrane fluidity [(1986) FEBS Lett. 194, 313-316] was employed to study the binding of specific ligands of the muscarinic receptor to rat brain membrane fragments containing a fluorescent analogue of phosphatidylcholine (APC) as a membrane probe. Upon addition of carbachol and atropine in low concentrations the fluorescence polarization of the APC-labeled membranes decreased significantly demonstrating that binding of these ligands to the muscarinic receptor increases the fluidity of its lipid environment. The fluidity changes were specific, concentration-dependent and saturable. In comparison with radioligand assays the fluorescent lipid probe method proved to be much more sensitive but the Kd values obtained by the two methods differed considerably.

Animals↗
PubMed1988

Diol lipids are activators of protein kinase C.

Diol lipids (dioleoyl- and dioctanoylethylene glycol) at relatively low concentrations (approximately 10 microM) were found to activate significantly protein kinase C in the presence of phosphatidylserine or phosphatidylinositol. Since diol lipids are widespread minor lipid constituents of many cells [(1974) Chem. Ind., 597-604], it has been suggested that they may be involved in the maintaining of basal protein kinase C activity in the absence of external stimuli.

Adenosine Triphosphate↗
PubMed1988

Interaction of influenza virus with gangliosides and liposomes containing gangliosides.

It has already been shown that influenza virus binds unspecifically to liposomes containing ganglioside GM1 wheras with gangliosides GD1b and GT1b binding occurs in a specific and saturable manner [Slepushkin et al. (1986) Biol. Membr. 3, 229-235]. In the present study the mode of interaction between influenza virus and various gangliosides or phospholipid liposomes containing cholesterol and gangliosides has been investigated. The influence of exogenous gangliosides on the structure of the viral envelope was studied using fluorescent and photoactivatable phospholipids incorporated into the viral membrane. With both types of probes maximal effects of gangliosides were caused by GT1b. Addition of that ganglioside resulted in a marked decrease in the fluorescence polarization (P) of fluorescent labeled virus as well as in substantial changes in the binding of photoactivatable analogues of sphingomyelin and phosphatidylcholine to virus proteins, mainly hemagglutinin. The effects of GT1b and GD1b on P value were comparable, whereas gangliosides with other oligosaccharide chains caused much smaller changes in P. Furthermore GT1b but not GM1 influenced phospholipid-hemagglutinin cross-linking. Interaction of the virus with large unilamellar liposomes was monitored by two fluorescence assays based on resonance-energy transfer from the tryptophans and tyrosines of viral proteins to vesicles labeled with a triacylglycerol (anthrylvinyldioleoylglycerol) or from these labeled vesicles to virions labeled with a perylenoyl derivative of galactosylcerebroside (PGalSph). A third fluorescence assay was based on relief of self-quenching in PGalSph-labeled virions, upon low-pH-induced virus-liposome fusion. With all three fusion assays the changes of fluorescence caused by GT1b were more pronounced than those induced by GM1. On the other hand, virus-induced release of [14C]glucose from multilamellar liposomes was enhanced by GM1 but not by GT1b or GD1b. It is concluded that the interaction of GT1b or GD1b with virus hemagglutinin induces a rearrangement of the viral lipids rendering lipid bilayer areas of the viral envelope significantly fluid, which in turn promotes fusion of the virus with target membranes. Probably virus-liposome fusion and virus-induced liposome leakage are brought about by different mechanisms depending on specific or unspecific binding of the virions to the target.

Binding Sites↗
PubMed1988

Stimulation of platelet adhesion and activation by ganglioside GD3 adsorbed to plastic.

Platelet interaction with gangliosides GD3, GM3, GM1, GD1a and GT1b has been investigated. These gangliosides were previously identified in the vessel wall and ganglioside GD3 was found to accumulate selectively in the intima of atherosclerotic vessels. Gangliosides were adsorbed to plastic and incubated with 51Cr-labeled platelets. The adhesion of gel-filtered platelets to ganglioside GD3 was 3-4 times higher than to other immobilized gangliosides and to albumin-treated plastic. As was shown by scanning electron microscopy, GD3 stimulated intensive spreading of adherent platelets and formation of surface-bound aggregates, while only single unspread platelets were present on the surfaces coated with other gangliosides. GD3 isolated from milk and from human aorta possess the same stimulating activity. Platelet adhesion to GD3 decreased significantly in the presence of the stable prostacyclin analogue, carbacyclin.

Adsorption↗
PubMed1987

The interaction of prostaglandins with high-density lipoproteins: a non-equilibrium model of ligand-receptor interaction.

Using high-density lipoproteins (HDL) labeled with a fluorescent phospholipid probe (an anthrylvinyl-labeled analogue of sphingomyelin) it was found that low amounts (10(-12) M) of the prostaglandins E1 and F2 alpha induced different structural changes of the HDL surface, whereas prostaglandin E2 had no effect. The effects of prostaglandin E1 on HDL were largely paralleled by those of this prostaglandin on synthetic recombinants prepared from apolipoprotein A1, phospholipids and cholesterol. The prostaglandin E1-HDL interaction resembled that of a ligand with a receptor site because it was specific, reversible, concentration- and temperature-dependent and saturable. However, the maximal HDL retaining capacity for prostaglandin E1 as determined by equilibrium dialysis was very low, and a single prostaglandin E1 molecule was able to induce structural changes in a large number of discrete lipoprotein particles. To explain this remarkable fact, a non-equilibrium model of ligand-receptor interaction is proposed. According to this model in open systems characterized by a short life-time of the ligand-receptor complex, high diffusion rates of the ligand and long relaxation times which exceed the interval between two successive ligand-receptor occupations, the ligand-induced changes will accumulate, resulting in amplification of the primary biological signal. 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.

Alprostadil↗
PubMed1987

The gangliosides of adult human aorta: intima, media and plaque.

The composition, structure and localization of gangliosides of aorta taken from subjects who had died after myocardial infarction were studied. Individual gangliosides were purified by high-performance liquid chromatography and high-performance thin-layer chromatography and were characterized on the basis of their chromatographic mobility, carbohydrate composition, neuraminidase hydrolysis and methylation analysis. The main aortic gangliosides were identified as GM3, GM1, GD3, GD1a and GT1b. Significant differences in the ganglioside composition of intima and media were detected and the ganglioside profile of atherosclerotic plaques was found to differ markedly from that of unaffected intima. The latter was characterized by high content of GD3, a ganglioside thought to be associated with membrane permeability, cell interaction, adhesiveness and growth and to suppress unspecific immune responses. Possible implications of the results in low-density lipoprotein binding to the arterial wall and in immunological changes induced by atherosclerotic lesions are discussed.

Adult↗
PubMed1987

Influence of prostaglandins on the lipid transfer between human high density and low density lipoproteins.

Prostaglandin (PG) E1 was demonstrated to stimulate the transfer of phosphatidylcholine and cholesterol esters from human high density lipoproteins (HDL3) to low density lipoproteins (LDL). The enhancement effect of PGE1 on the interlipoprotein lipid transfer was seen at low PG concentrations under conditions of spontaneous exchange as well as in the presence of lipoprotein-depleted plasma, or partly purified plasma lipid exchange protein. PGE2 and PGF2 alpha showed no significant influence on the interlipoprotein lipid transfer. Evidence is presented suggesting that the PGE1-induced stimulation of interlipoprotein lipid exchange results in enhancement of LCAT-catalyzed cholesterol esterification in plasma. It is proposed that the effect of PGE1 is due to the previously described PGE1-induced reorganization of the HDL surface [(1984) FEBS Lett. 173, 291-293] and that PG-lipoprotein interaction may be a factor regulating cholesterol homeostasis.

Alprostadil↗