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L D Bergelson

Publications and source records attributed to L D Bergelson.

At least 19 recordsLinked to original sources
PubMed1998

The down-modulation of CD4 induced by the GM1 ganglioside is regulated by phosphatases and kinases: evidence from enzyme inhibitors and anti-CD45 antibodies.

The involvement of protein kinases and phosphatases in the down-modulation of expression of CD4 molecules on peripheral blood lymphocytes (PBL) by gangliosides was studied. Exposure of PBL either to genistein or to H7 practically abolished the down-modulation of CD4 induced by GM1 and diminished their susceptibility to CD4+ down-modulation by exposure to GD1a. Staurosporine had no effect on the down-modulation of CD4 by either GM1 or GD1a. Orthovanadate treatment drastically inhibited the down-regulation of CD4 induced by GM1 but had no effect on down-modulation of CD4 induced by GD1a. Exposure to monoclonal antibodies (mAbs) against CD45 and CD45RA but not against CD45RO abrogated the down-modulation of CD4 by GM1. The down-modulation of CD4 elicited by GD1a, GD1b, or GT1b was not inhibited by anti-CD45RA and anti-CD45RO mAbs. MAbs against CD3, CD2, or HLA-DR had no effect on the GM1-induced down-modulation of CD4. In view of the differences obtained between GM1 and GD1a it was of interest to check whether these gangliosides competed for cellular binding sites. When PBL were first treated with anti-CD45RA and GM1 or with orthovanadate and GM1, which had a negligible effect on CD4 expression, and subsequently treated with GD1a the expression of CD4 was down-modulated. This demonstrated that GD1a binds to sites on the cell membrane to which GM1 does not bind. The present study indicates that the capacity of GM1 to down-modulate CD4 depended on the CD45 and particularly CD45RA molecules, while other gangliosides may utilize different cell surface structures to down-modulate the expression of CD4.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Autoantibodies to gangliosides in sera of atherosclerotic patients.

Using ELISA we studied the levels and clinical correlation of serum antibodies against gangliosides and 5-hydroxytryptamine (5-HT) in patients with atherosclerosis and clinical manifestations of cardiovascular disease. A range of 70-80% of the patients showed higher titers of anti-GM3(L) and anti-5HT as compared to normal serum. The anti-GM3(L) antibodies appeared to be directed mainly against GM3 present in platelets and were much less reactive against GM3 isolated from the aorta. We concluded that the antigens responsible for the elevated anti-GM3(L) and anti 5-HT levels in atherosclerotic sera are released by vessel-wall activated platelets. These results provide further evidence of on-going autoimmune processes in atherosclerosis. The content of total sialic (TS) and lipid-bound sialic acid (LBS) was measured in sera of patients with IHD and of similar numbers of healthy donors. In the patient groups the average TS and LBS concentration was about 25% higher than in the control group. These changes appeared to be associated with higher degrees of protein sialylation and larger amounts of LDL in the patient sera than in those of healthy controls.

Adult↗
PubMed1997

Nanomolar concentrations of gangliosides stimulate primary humoral response.

Exogenous gangliosides act as immunosuppressors when applied at micromolar concentrations corresponding to their average level in human plasma. Here we show that at nanomolar concentrations the gangliosides GD3, GD1a and GM1 can act as immunostimulators markedly enhancing the number of plaque-forming cells in mouse splenocyte culture responding to sheep erythrocytes. At such low concentration these gangliosides as well as GM3 were not able to influence significantly proliferative responses of splenic B and T lymphocytes or of cytotoxic T-cells. Neither did they change significantly the production of IL-1 by antigen- representing cells, or of IL-2 by Con A-induced blasts in the splenocyte culture. It is suggested that the stimulatory effect of low ganglioside concentrations on humoral response is due to their influence on cooperative cell-cell interactions required for the differentiation of B-cells into Ig-secreting cells.

Adjuvants, Immunologic↗
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↗
PubMed1994

Anthrylvinyl-labeled phospholipids as membrane probes: the phosphatidylcholine-phosphatidylethanolamine system.

The phase behavior of mixtures of phosphatidylcholine (PC) with phosphatidylethanolamine (PE) identical or differing in their fatty acid composition has been investigated by using the steady-state fluorescence anisotropy of anthrylvinyl-labeled PC and PE (APC and APE) as well as of the non-lipid probe 1,6-diphenyl-1,3,5-hexatriene (DPH) to detect temperature-dependent changes in multilayer liposomes. APC, but not APE, was able to detect the pretransition of dimyristoyl-PC. The phospholipid probes APC and APE showed the main phase transition of their unlabeled disaturated analogues at temperatures almost identical with those revealed by differential scanning calorimetry, whereas the onset of the PE phase transition recorded by DPH was several degrees higher. In PC-PE mixtures with high content of PE the phase transitions shown by APC and APE were broader than those recorded by DPH. Comparison of phase diagrams constructed on the basis of fluorescence anisotropy and calorimetric data led to the conclusion that in biphasic PE and PC-PE systems DPH tends to partition into solid regions, whereas the anthrylvinyl-labeled phospholipids distribute more evenly between coexisting phases or prefer fluid domains. The use of anthrylvinyl phospholipid probes made it possible to demonstrate that PEs and PCs identical in their fatty acids are not miscible completely, not only below but also well above Tm of the higher melting component. Generally, APC and APE fluorescence anisotropy measurements correctly reflect headgroup-dependent phase segregations in mixtures of PC with PE, but may lead to ambiguous conclusions if demixing is caused by differences in the hydrocarbon chains.

Chemical Phenomena↗
PubMed1994

Gangliosides and atherosclerosis.

The ganglioside levels in atherosclerotic lesions of human aorta are considerably higher than those in unaffected areas of aorta, and atherosclerotic patients frequently have increased concentrations of serum gangliosides. The present review summarizes recent findings that suggest the possible involvement of aortic gangliosides in platelet activation and adhesion of platelets to the vessel wall. The effect of gangliosides on the structure of low density lipoproteins (LDL), on the interaction of LDL with macrophages and hepatic cells and on the LDL-regulated biosynthesis of cholesterol is also discussed. In vitro experiments have demonstrated that a major ganglioside of the intima of atherosclerotic aorta induces rapid adhesion, aggregation and spreading of platelets. Moreover, gangliosides present in elevated amounts in the intercellular space of atherosclerotic aortic tissue modify the surface structure and stimulate aggregation of LDL. Ganglioside-modified LDL are readily recognized and taken up by macrophages, while preincubation of LDL with low concentrations of gangliosides inhibits LDL binding to hepatic cells. Thus, ganglioside enrichment of LDL is likely to interfere with LDL clearance via the hepatic cells. Thus, ganglioside enrichment of LDL is likely to interfere with LDL clearance via the hepatic LDL receptor, and to stimulate binding of LDL to the scavenger receptor of macrophages. It is postulated that high ganglioside levels in the aorta and serum may be an additional risk factor in atherosclerosis.

Arteriosclerosis↗
PubMed1993

Interaction of peptide fragment 828-848 of the envelope glycoprotein of human immunodeficiency virus type I with lipid bilayers.

The interaction of the peptide fragment 828-848, called P828, from the carboxy-terminal region of the envelope glycoprotein gp41 of HIV-I with model membranes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) was investigated using microelectrophoretic mobility of liposomes, fluorescence polarization of labeled lipids, NMR, and differential scanning calorimetry. The peptide binds to negatively charged lipid surfaces. No interaction between P828 and neutral PC surfaces is observed. The interaction between the peptide and the lipid is exclusively electrostatic with the six positively charged arginines of P828 acting as binding sites for PG. Circular dichroism measurements of P828 indicate that the peptide undergoes a transition from a random coil to an ordered conformation upon binding to negatively charged PG bilayers or SDS micelles, but not in the presence of neutral PC bilayers. The ordered structure has an apparent helical content of 60%. IN DOPG/DOPC mixtures containing 20 mol % DOPG, the peptide causes the formation of lipid domains enriched in DOPG, as assessed by measurement of fluorescence energy transfer between labeled PG and PC. The formation of these domains requires energy and therefore reduces the strength of peptide binding to the lipid matrix. Our data support and quantitate the results from antibody binding studies [Haffar, O.K., Dowbenko, D. J., & Berman, P. W. (1988) J. Cell Biol. 107, 1677-1687] that the carboxy-terminal segment of the envelope glycoprotein gp41 interacts with microsomal membranes.

Amino Acid Sequence↗
PubMed1993

Nanomolar concentrations of prostaglandin E1 induce changes in the surface organization of high-density lipoproteins.

Incubation of high-density lipoproteins (HDL) with small amounts of the prostaglandin E1 (PGE1) results in mobilization of the spin-label 5-doxylstearic acid incorporated into the HDL surface monolayer as well as in decreased binding of apoprotein A1 antibodies to the HDL surface. These effects are manifested at strikingly low PGE1 concentrations, corresponding to one prostaglandin molecule per 10(2)-10(3) lipoprotein particles. At the same time, the flotation properties of HDL are not changed in the presence of PGE1. The data are interpreted on the basis of a nonequilibrium model proposed earlier for prostaglandin-lipoprotein interactions (Bergelson, L. D., et al. (1987) Biochim. Biophys. Acta 921, 182-190).

Alprostadil↗
PubMed1993

Gangliosides and antitumor immunity.

To elucidate the possible influence on the host's immune defense of circulating gangliosides released from tumor cells, the effects of exogeneous gangliosides on the activities of some lymphocyte subpopulations were examined. The mono- and disialyllactosylceramides GM3 and GD3, which frequently are present in elevated amounts in sera of tumor-bearing hosts, were found to inhibit strongly the cytotoxicity of natural killer cells, to stimulate T-suppressor activity of peripheral blood lymphocytes, and to inhibit their phytohemagglutinin-induced blast transformation. All these effects may be linked to the ability of gangliosides to modulate the arachidonic acid cascade in lymphoid cells, which for the first time was demonstrated in the course of our studies. Possible mechanisms underlying the immunomodulatory effects of serum gangliosides as well as their role in the escape of tumor cells from immune surveillance and inhibition of the hosts immune system are discussed.

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↗