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PubMed1975

Modulation of the immune response by antigen-reactive lymphocytes after cultivation with gangliosides.

GM1 ganglioside isolated from mouse brain was found to be capable of inhibiting the thymocytotoxicity of AKR anti-Thy 1.2 antiserum and to a lesser extent anti-BAtheta antiserum. GD1b ganglioside of mouse brain and thymocytes inhibited the thymocytotoxicity of rabbit anti-BAtheta anti-serum for mouse thymocytes. When GM1 ganglioside, in the form of cholesterol-lecithin liposomes, was incubated with spleen cell cultures in the presence of SRBC, depressed anti-SRBC hemolytic plaque responses were observed. This effect could be neutralized by first absorbing the GM1 liposomes with anti-Thy-1.2 antibodies. The kinetics of GM1 numbers when the ganglioside was added even as late as the 4th day of culture. Results of experiments in which GM1 ganglioside was incubated with either bone marrow cells or with thymocytes suggest that the target cell for GM1 liposomes is the B lymphocytes.

Animals↗
PubMed2000

Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan.

To clarify the relations of the axonal form of Guillain-Barré syndrome (GBS) to anti-ganglioside antibodies and Campylobacter jejuni infection, 86 consecutive Japanese GBS patients were studied. Electrodiagnostic criteria showed acute inflammatory demyelinating polyneuropathy in 36% of the patients and acute motor axonal neuropathy (AMAN) in 38%. Frequent anti-ganglioside antibodies were of the IgG class and against GM1 (40%), GD1a (30%), GalNAc-GD1a (17%), and GD1b (21%). Identified infections were C. jejuni (23%), cytomegalovirus (10%), Mycoplasma pneumoniae (6%), and Epstein-Barr virus (3%). There was a strong association between AMAN and IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b. Almost all the patients with at least one of these antibodies had the AMAN pattern or rapid resolution of conduction slowing/block possibly because of early-reversible changes on the axolemma. C. jejuni infection was frequently associated with AMAN or anti-ganglioside antibodies, but more than half of the patients with AMAN or anti-ganglioside antibodies were C. jejuni-negative. These findings suggest that the three phenomena "axonal dysfunctions (AMAN or early-reversible conduction failure)," "IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b," and "C. jejuni infection" are closely associated but that microorganisms other than C. jejuni frequently trigger an anti-ganglioside response and elicit axonal GBS.

Adolescent↗
PubMed2001

Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function.

Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common extracranial solid tumor in children. NB-derived gangliosides inhibit the functional activity of T and natural killer cells, contribute to tumor-induced bone marrow suppression, and cause multiple alterations of hematopoiesis, resulting in pancytopenia. However, the role of gangliosides in the regulation of dendritic cell (DC) generation (dendropoiesis) has not been studied. Using murine and human NB cell lines, we demonstrated that coincubation of murine bone marrow progenitors or human CD34+ progenitor cells with NB cells resulted in a significant inhibition of dendropoiesis in vitro up to 90%. The number of DCs was assessed by FACScan determination of CD83+ or CD11c+ cells coexpressing MHC class II and CD86 molecules. In addition, inhibition of antigen-presenting properties of DCs cultured in the presence of NB cells was observed in allogeneic mixed leukocyte reaction (33,508 +/- 1,613 cpm for control DCs versus 17,428 +/- 152 cpm for NB-treated DCs; P < 0.05). Treatment of NB cells with 10 microM DL-threo-1-phenyl-2-decanolylamine-3-morpholino-1-propanol HCl, an inhibitor of glucosylceramide synthase, markedly abrogated ganglioside synthesis and was accompanied by blockade of NB ability to inhibit dendropoiesis. Furthermore, purified gangliosides added to DC cultures significantly inhibited DC generation. The percentage of CD83+ cells decreased from 51.8 +/- 6.1% in the control group to 12.9 +/- 2.7% in cultures treated with GD2 (P < 0.05). Thus, our results demonstrate that NB-derived gangliosides inhibit the generation of functionally active DCs and may play a role in tumor-induced immunosuppression and subsequent tumor escape from immune recognition and elimination.

Animals↗
PubMed2000

Suppression of Ehrlich ascites tumor growth by immunization with ganglioside GT1b of its origin, its IgM antibody or anti-idiotype of the anti-GT1b IgM.

Ehrlich tumor expresses the ganglioside GT1b. The plasma of mice with Ehrlich ascites tumor burden also contains GT1b. The structural identity of plasma GT1b was ascertained by a series of enzymatic degradation and mass spectral analysis. Mice were vaccinated with purified plasma GT1b admixed with Freund's adjuvant (FA). Sixty nine percent suppression of Ehrlich ascites tumor growth was observed in vaccinated mice. The suppression was dose-dependent. It is hypothesized that the tumor growth-suppression is a result of immune response to GT1b Humoral immune response to GT1b was demonstrated by passive hemagglutination assay of the sera of vaccinated mice. To test the hypothesis, the mice were administered with rabbit polyclonal anti-GT1b IgM antibody in varying doses and challenged with Ehrlich tumor. A significant reduction in tumor growth (65%) was observed in mice administered with anti-GT1b IgM antibody. Again, the suppression was dose-dependent. To verify further, another batch of mice was immunized with anti-idiotypic antibodies to rabbit anti-GT1b IgM raised in rat. The polyclonal anti-idiotype antibody is expected to carry the structural image of GT1b. In a dose-dependent manner, a maximum of 82% suppression of tumor growth was observed in mice immunized with the anti-idiotype antibody. This observation further strengthened the hypothesis that ganglioside mediated suppression of tumor growth may be a result of immunogenicity of the target ganglioside. This was also supported by positive reaction of the sera of anti-idiotype vaccinated mice with both anti-idiotype antibody and ganglioside GT1b in passive hemagglutination assay. The results favour the therapeutic potential of immunogenic tumor-associated gangliosides.

Animals↗
PubMed1979

[The complexing ability of gangliosides for Ca2, I. Influence of mono- and divalent cations and of acetylcholin (author's transl)].

The binding of Ca2 to single ganglioside species (GGtet1NeuAc, GGtet2aNeuAc, GGtet 3aNeuAc), to their free, reducing sialyl-oligosaccharides and to ganglioside mixtures from chicken brain was investigated by means of ion-sensitive electrodes (potentiometry). Unlike the sialyl-oligosaccharides and free N-acetylneuraminic acid, gangliosides were found to possess two different modes of binding for Ca2, depending on the total concentration of Ca2. This was mainly indicated by a release of up to 75% of previously bound Ca2 after raising the total Ca2-concentration above a critical level of about 5--9 X 10(-5)M. Addition of acetylcholin (9mM), Li, K, and Na, respectively, caused a release of Ca2 from ganglioside-Ca2-complexes (0.1mM Ca2, 0.1mM ganglioside-NeuAc) in the sequence: acetylcholin : Li : K : Na = 4 : 3 : 1 : 1 composed on molar basis (9mM).

Acetylcholine↗
PubMed2000

Study on ganglioside composition in brain tumours supra- and infratentorial.

The composition of gangliosides in primary tumors depends on their histological origin and differentiation grade (biological malignancy). The aim of the present study was the comparison of gangliosides in various types of brain tumours. The studies were performed on specimens from 20 high grade gliomas, 5 low grade gliomas, 8 meningiomas and 9 metastatic tumours. The isolated gangliosides were separated on silica 60 HPTLC plates and their mobilities were compared with glycolipids standards. The following observations were made: 1. high and low grade gliomas had similar ganglioside profiles comprising 7 different species; 2. the profiles of gangliosides isolated from metastatic neoplasms differ considerably from those of gliomas as well as menigiomas.

Adult↗
PubMedDate not supplied

[Gangliosides in neurological pharmacotherapy].

Gangliosides take part in synaptic transmission, neuronal metabolism and development of nervous tissue. They cooperate with nerve growth factor (NGF) and have positive influence on regeneration of the nervous system impairments. There exist many behavioural and biochemical evidences of gangliosides participation in the regeneration of experimentally injured animal nervous system. The therapeutic effectivity of gangliosides in clinical practice is encouraging. Commercial preparates of gangliosides (Cronassial, Sygen) have been successfully used in the therapy of chronic neuropathies, strokes and subarachnoidal haemorrhages. Among the adverse reactions to these drugs are: local irritation, anxiety and possible detrimental effect in immunological system. Ganglioside preparations need further clinical examinations.

Brain↗
PubMed1992

Antibodies against gangliosides in patients with SLE and neurological manifestations.

Pathogenesis of neuropsychiatric manifestations of systemic lupus erythematosus (SLE) has not been clearly defined, and the search for pathogenic mechanisms has focused on the importance of several autoantibodies. There is increasing evidence that antibodies against gangliosides may have a pathogenic role in some neurological disorders. The aim of the present study was to examine the association between antibodies against gangliosides and neuropsychiatric SLE. We found anti-type II ganglioside antibodies in two out of 32 patients with multiple sclerosis (6.25%) and in 10 out of 60 patients with SLE (16.6%); five of 17 patients with neurological abnormalities also had high levels of these antibodies (29.4%). Five of the 10 patients with SLE and positive antiganglioside antibody had only IgM antibodies, three had IgG antibodies and two had both isotypes. By chi-square analysis, the incidence of anti-type II ganglioside antibodies was not significantly higher in patients with symptoms related to the nervous system than in SLE patients without neurological involvement (P > 0.2). No clear correlation was found between antibodies against gangliosides and cardiolipin.

Adolescent↗
PubMedDate not supplied

[The effect of exogenous gangliosides on the dynamics of the development of prolonged posttetanic potentiation].

In hippocampal slices of rats was studied the influence of different gangliosides on the dynamics of development of long-term post-tetanic potentiation (LPTP) in the pyramidal cell layer of the CA3 area at stimulation of the mossy fibers. Each ganglioside was shown to change synaptic efficiency specifically after the tetanic stimulation. Incubation of hippocampal slices with monosialoganglioside GM1 induced the rapid increase of population spike amplitude in the pyramidal neurons being of higher level in comparison to that of the active control up to the end of the experiment. Disialoganglioside GD1b increased the amplitude of the summary cellular response to a lesser degree than GM1, but contributed to its conservation up the control level in the course of the whole recording period. Gangliosides GD1a and GT1b induced inhibitory action on LPTP decreasing population spike value lower than that of both the control and initial levels, GT1b causing more rapid decrease of amplitudes of cellular responses than GD1a. A conclusion was drawn on the participation of gangliosides in the mechanisms of synaptic plasticity. The differential influence of various kinds of gangliosides on the LPTP dynamics was found out. The possible mechanisms of these reactions are discussed.

Action Potentials↗
PubMed1992

A novel ganglioside expressed by mouse hematopoietic cell lines.

Mouse progenitor T cell-derived cell lines were established by fusion of cells of hematopoietic organs such as bone marrow and fetal liver with T lymphoma (BW5147) to determine their characteristic cell-surface components. The hybridomas with the phenotype of Thy-1+, CD3-, CD4-, CD8- and expression of T cell receptor gene mRNA (BM216 and FL339) were selected for progenitor T cell-derived cell lines, and their ganglioside compositions were studied. A ganglioside component with a mobility slightly faster than that of bovine brain GD1a on high-performance thin-layer chromatography was found in the cell extracts of these cell lines as one of the most abundant components and was absent in the extract of the parental cell line (BW5147). The structure of the ganglioside was determined to be: NeuAc alpha-Gal beta-Gal beta-Gal alpha-Gal beta-Glc beta-ceramide. Gangliosides with such a sequence have never been found before, suggesting the possibility that the ganglioside is expressed as a surface marker of the cells in hematopoietic organs committed to a specific cell lineage, presumably to T cell lineage. cells in hematopoietic organs committed to a specific

Animals↗
PubMed1992

[Multifocal motor neuropathy after administration of gangliosides].

A case of a 38 years-old male with motor neuropathy with multifocal conduction blocks following the administration of ganglioside therapy is reported. There was generalized weakness without areflexia and normal parameters of the spinal fluid, including protein values. Electrophysiological data showed multiple conduction blocks with normal nerve conduction velocities. Antibodies against asialo-GM1 gangliosides were present in the cerebrospinal fluid. There could be a relationship between the ganglioside administration and the development of an immune-mediated neuropathy. Several cases of demyelinating polyradiculoneuritis after ganglioside treatment have been reported. If this association is confirmed, the apparent lack of toxicity of gangliosides should be reconsidered.

Adult↗
PubMed2004

Incorporation, remodeling and re-expression of exogenous gangliosides in human cancer cell lines in vitro and in vivo.

Human neuroblastomas and gliomas express high levels of GD2 ganglioside. Mechanisms for the re-expression of GD2 after the incorporation of an exogenous precursor structure were analyzed using a human heterophilic monoclonal antibody (mAb) together with mouse anti-GD3 and mouse anti-GD2 mAbs. First, mouse anti-GD2 mAb 220-51 was generated and its reactivity was confirmed to be almost identical with that of the well-known mAb 3F8 antibody. As reported previously for GD3 variants, new ganglioside antigens reactive with human mAb 32-27 were analyzed by culturing an astrocytoma cell line AS in the presence of NeuGc-GM3. Analysis of the extracted gangliosides from AS thus cultured revealed a new component detected with mAb 32-27, migrating similarly to GD2. Incorporated NeuGc-GM3 seemed to be converted to NeuAc-NeuGc-type GD3, and then to NeuAc-NeuGc-type GD2 with alpha2,8-sialyltransferase and beta1,4-GalNAc transferase, respectively. In addition, AS was inoculated into nude mice, and glycolipids were extracted from generated tumors. Analysis of the ganglioside components using mAbs indicated that NeuAc-NeuGc-type GD2 was generated in the xenogeneic tumors by incorporating NeuGc-GM3 from mouse blood. These results indicated the presence of a pathway for utilization of exogenous gangliosides for remodeling and re-expression in vivo.

Animals↗
PubMedDate not supplied

Ganglioside (GD2) expression and intermediary filaments in astrocytic tumors.

The search of proliferation markers in astrocytic tumors that may serve as targets for therapeutic interventions, is in full progress. Membrane-bound signal transducers for growth factors are amongst the substances of interest. Gangliosides are lipid-sugar compounds localized on the cell membrane that are thought to modify pertinent signals and, therefore, may influence a variety of functions in normal and pathologic conditions including those that act upon tumor growth. Intracranial supratentorial astrocytic gliomas of the adult represent a tumor group, that may be divided into three grades of malignancy, the most anaplastic member being the glioblastoma. A stepwise anaplasia is assumed and accompanied by genetic events that are partly specific for these grades. In earlier investigations, it had been shown that there is a tendency towards formation of more simple members of the ganglioside family with ongoing malignancy of those tumors. Yet, the results were only partly congruent and the correlation to tumor grades rather loose. We, therefore, investigated the occurrence of triaose gangliosides within these tumors in situ by immunohistochemistry. In this paper, we corroborate our earlier observation that triaose gangliosides preferentially occur within the cytoplasm of large protoplasmic and gemistocytic astrocytes. The potency of the expression of GD2 is calculated and plotted against the expression of two markers of intermediate glial filaments, namely GFAP (glial fibrillary acid protein) and vimentine. A high interdependence of the three compounds could be demonstrated by correlation analysis. Thus, the conclusion must be drawn that the correlation of ganglioside patterns to the proliferation of astrocytic tumors is as poor as that of GFAP or vimentin expression, respectively.

Aged↗
PubMed1991

Gangliosides administration causes sugar moiety-specific enzymatic changes in brain.

Exogenous gangliosides are known to affect the metabolism when administered to the body. To study the mechanism of this effect three types of gangliosides were administered intraperitoneally to mice and the changes in the enzyme activity of the cerebral tissues studied. The effect of GM2 from bovine brain was characterized by a decrease in the activity of various aminopeptidases, while GD3 from cow's milk caused an increase in the activity of sugar-related enzymes such as sialidase, glucosidase, and fucosidase. GM3 from horse erythrocytes showed intermediate effects between GM2 and GD3. Multivariate analysis showed that the effects of the three gangliosides are clearly separable statistically. These results which demonstrate the sugar moiety-specificity of gangliosides are discussed in relation to the A and B pathways of ganglioside synthesis.

Amino Acid Sequence↗
PubMed1991

The effect of bovine brain gangliosides on essential tremor.

We reported the case of a 74-year-old woman suffering from essential tremor for 20 years which was treated effectively with purified bovine brain gangliosides containing GM1, GD1a, GD1b and GT1b gangliosides. The trials of the treatment were conducted twice, 40 mg and 20 mg gangliosides per day respectively administered intramuscularly. Essential tremor dramatically improved with gangliosides on the second day of treatment, suggesting that the effect of gangliosides was not induced by neuronal sprouting or regeneration. It is speculated that a certain type of essential tremor is a reversible disease of membrane disorder.

Aged↗
PubMed1990

Northern hybridization analysis of VH gene expression in murine monoclonal antibodies directed to cancer-associated ganglioside antigens having various sialic acid linkages.

The expression of the VH genes in 46 murine hybridoma cells that secrete mAb directed to the cancer-associated carbohydrate Ag, especially acidic glycolipids such as gangliosides and sulfated glycoplipids, was analyzed by Northern hybridization of poly(A)+ RNA of hybridoma with cDNA probes for nine VH gene families. Different hybridomas tended to express VH genes of the same family when the cognate Ag had the same or similar carbohydrate structures; i.e., the VH genes of the J558 family (group 1) were preferentially expressed in the mAb directed to various gangliosides that have NeuAc alpha (or NeuGc alpha) 2-3 and/or 2-8 linkage (71%), the most common linkage of sialic acid residues in the gangliosides of higher animals, and the hybridomas directed to sulfated glycolipids also expressed mainly the VH genes of the J558 family (80%). In contrast, the five mAb directed to various gangliosides with NeuAc alpha 2-6 linkage were exclusively encoded by the VH genes of Q52 family (group 2, 100%), and three antibodies directed to gangliosides with a NeuAc alpha 2-9 linkage all expressed genes of J606 family (group 6, 100%). The VH family usage was largely correlated with the linkage of sialic acid residues in the cognate carbohydrate Ag, but was not correlated at all with the difference in the fine specificities toward the core neutral carbohydrate chain, to which the sialic acid residues were attached. These findings suggest that the VH gene family in these anticarbohydrate antibodies is selected, depending primarily on the linkage of the sialic acid residues in carbohydrate Ag; these residues form the immunodominant sugar residue in the respective antigenic determinant.

Animals↗
PubMed1990

[The effect of gangliosides on the adhesive interaction of Neisseria meningitidis with human cells].

The influence of a number of gangliosides and sialic acid on the adhesive interaction of meningococci and human cells have been studied. Sialic acid has been found to produce no influence on adhesion, and the preliminary treatment of meningococci with gangliosides or their preparations suppresses the capacity of meningococci for attachment to epithelial cells and erythrocytes. At the same time the degree of the inhibition of adhesion depends on the kind and concentration of gangliosides. On the contrary, after the treatment of target cells with gangliosides (1.25 micrograms/ml) the adhesion indices of meningococci with respect to these cells increase 5- to 8-fold. These data are indicative of the participation of gangliosides in the adhesive interaction of meningococci and human cells.

Animals↗
PubMed1990

pH-dependent changes of ganglioside biosynthesis in neuronal cell culture.

Ganglioside biosynthesis was studied in primary cultured murine cerebellar cells after labeling with [14C]galactose. A shift in biosynthesis from "a"-series to "b"-series gangliosides was observed after lowering the pH of the culture medium from 7.4 to 6.2; this effect was fully reversible on changing back to pH 7.4. The observed regulatory effect of pH is in accordance with a recent model of ganglioside biosynthesis. Sialyltransferase II (ST II), the first enzyme for biosynthesis of "b"-series gangliosides, is more active at pH 6.2 than Gal-NAc-transferase, the first enzyme for synthesis of "a"-series gangliosides, which is more active than sialyltransferase II at pH 7.4.

Animals↗