GD 1a Research Articles

From Monomeric Species to One-Dimensional Chain: Enhancing Slow Magnetic Relaxation through Coupling Mononuclear Fragments in Ln-rad System

By reacting nitronyl nirtroxide radical NIT-Ph2OEt (NIT-Ph2OEt = 2-(2′-ethoxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) with Ln(hfac)3(hfac = hexafluoroacetylacetonate), four new Ln–nitronyl nitroxide complexes, namely, mononuclear species [Ln(hfac)3(NIT-Ph2OEt)2](LnIII = Gd 1a, Tb 1b) and one-dimensional chains [Ln(hfac)3(NIT-Ph2OEt)]n (LnIII = Gd 2a, Tb 2b), have been successfully obtained through controlling the reaction temperature and the ratio of radical ligand and Ln(hfac)3. DC magnetic susceptibilities indicate that the ferromagnetic couplings occur between the coordination radicals and the Ln(III) ions for four complexes. No nonzero out-of-phase signals are observed for mononuclear segment 1b, whereas the corresponding 1D chain 2b exhibits frequency-dependent out-of-phase signals indicating single-chain magnet behavior, which implies that the intrachain next-nearest-neighbor (NNN) Ln—Ln magnetic interactions play a crucial role for enhancing slow magnetic relaxation in the chain. More...

Heterometallic Tetranuclear [LnIII2CoIII2] Complexes Including Suppression of Quantum Tunneling of Magnetization in the [DyIII2CoIII2] Single Molecule Magnet

Using a heterometallic approach the synthesis, structures, and magnetic properties are reported for the complexes [Ln(III)(2)Co(III)(2)(OMe)(2)(teaH)(2)(O(2)CPh)(4)(MeOH)(4)](NO(3))(2)·MeOH·H(2)O {Ln = Gd (1a), Tb (2a), and Dy (3a)} and [Ln(III)(2)Co(III)(2)(OMe)(2)(teaH)(2)(O(2)CPh)(4)(MeOH)(2)(NO(3))(2)]·MeOH·H(2)O {Ln = Gd (1b), Tb (2b), and Dy (3b)}. Both compounds for the respective lanthanide ions are found to be isolated within the same crystal. Each Ln(III) dinuclear unit is incorporated within a diamagnetic Co(III)/organic ligand backbone utilizing triethanolamine and benzoic acid as bridging ligands. Magnetic studies reveal an absence of any observable coupling interaction for the Gd case. The Dy analogue displays single molecule magnet (SMM) behavior with a large energy barrier to magnetization reversal of 88.8 K, and the quantum tunneling of the magnetization (QTM) is effectively suppressed because of the nonmagnetic exchange ground state of the molecule. Dilution of the Dy complex into an isostructural diamagnetic yttrium matrix allowed us to determine aspects of the relaxation mechanism within the system.

Interaction of siglec protein with glycolipids in a lipid bilayer deposited on a gold electrode surface

Unsymmetric three component lipid bilayers containing 1,2-dimyristoyl- sn-glycero-3-phosphatidylcholine (DMPC), cholesterol and a ganglioside were prepared using the Langmuir–Blodgett–Langmuir–Schaefer (LB–LS) technique on the surface of a polycrystalline gold electrode. The lipid layer contains the ganglioside only in the outer layer, mimicking a natural cell membrane. Gangliosides are glycolipids containing at least one sialic acid residue and are proposed to be a binding partner for siglec proteins. Interaction between Siglec-4, the myelin-associated glycoprotein (MAG) and two gangliosides in lipid bilayers was investigated. MAG protein binds only to the sialic acid residue located at the terminal position in the oligosaccharide head group of a lipid molecule. In this study two gangliosides, the GD 1a having one terminal sialic acid residue and the GM 1 not possessing a terminal sialic acid residue in the polar head group were used. Under physiological conditions a lipid membrane is constantly exposed to high electric fields. Three component lipid bilayers transferred by the LB–LS method are characterized by capacitance minimum equal to 2.3 and 5.0 μF cm −2 in the film containing the GM 1 and GD 1a, respectively. The lipid bilayer desorbs form the electrode surface at E < −0.8 V vs. Ag|AgCl. The potential driven adsorption–desorption process is irreversible and leads to an increase in the capacitance of the adsorbed lipid films. The lipid films undergo some irreversible changes which may lead to a flip–flop of bilayer fragments, formation of micelles on the electrode surface or decrease in surface coverage. Exposure of the bilayer to the protein solution stabilizes lipid films adsorbed directly on the electrode surface. The potential induced adsorption of the bilayer containing the GD 1a in the presence of the protein hinders structural changes taking place in the lipid film exposed to changing electric fields. At the molecular level the binding of the protein to the GD 1a introduces structural changes not only in the glycolipid molecule, but in the whole membrane. In the polar head group of the GD 1a amide groups in sialic acid residues lose some water of hydration upon interaction with the protein. The hydrocarbon chains of the GD 1a exhibit ordering with respect to the surface normal. Reorientations in the ganglioside molecule may lead to changes in the phosphatidylcholine, main lipid component of the bilayer. In the DMPC molecule the dehydration of the ester group with simultaneous change in tilt of the acyl chains were observed.

Liquid Chromatography–High‐Resolution Mass Spectrometry for Quantitative Analysis of Gangliosides

Gangliosides are a large family of glycosphingolipids that are abundant in the brain, and have been shown to affect neuronal plasticity during development, adulthood, and aging. We developed a fast, efficient, and sensitive liquid chromatography-mass spectrometry method to quantify eight different classes of gangliosides (GM(1), GM(2), GM(3), GD(3), GD(1a), GD(1b), GT(1b), GQ(1b)) in the brains of 2-day-old and 80-day-old Wistar rats. The gangliosides were extracted from rat brain using a modified Svennerholm and Fredman method. After ganglioside class separation using a hydrophilic high performance liquid chromatography (HPLC) column, the resolving power of the LTQ-Orbitrap mass spectrometer was used to extract and sum the major species of each ganglioside class, generating fully resolved extracted ion current peaks for both standards and samples. The flexibility and the specificity of this method are such that it can be applied to the analysis of other ganglioside species/classes not discussed in this paper, provided appropriate standards are available. The method had good repeatability (coefficient of variation 4.8-12.3%) and mean recoveries in the range 92-107%.

Ferromagnetic coupling in the three-dimensional malonato-bridged gadoliniumIII complex [Gd2(mal)3(H2O)6] (H2mal = malonic acid).

The novel gadolinium(III) complex of formula [Gd(2)(mal)(3)(H(2)O)(6)] (1) (H(2)mal = 1,3-propanedioic acid) has been prepared and characterized by X-ray diffraction analysis. Crystal data for 1: monoclinic, space group I2/a, a = 11.1064(10) A, b = 12.2524(10) A, c =13.6098(2) A, beta = 92.925(10) degrees, U = 1849.5(3) A(3), Z = 4. Compound 1 is a three-dimensional network made up of malonate-bridged gadolinium(III) ions where the malonate exhibits two bridging modes, eta(5)-bidentate + unidentate and eta(3):eta(3) + bis(unidentate). The gadolinium atom is nine-coordinate with three water molecules and six malonate oxygen atoms from three malonate ligands forming a distorted monocapped square antiprism. The shortest metal-metal separations are 4.2763(3) A [through the oxo-carboxylate bridge] and 6.541(3) A [through the carboxylate in the anti-syn coordination mode]. The value of the angle at the oxo-carboxylate atom is 116.8(2) degrees. Variable-temperature magnetic susceptibility measurements reveal the occurrence of a significant ferromagnetic interaction through the oxo-carboxylate pathway (J = +0.048(1) cm(-1), H = -JS(Gd(1)) x S(Gd(1a))).

A potentially important excretory–secretory product of Giardia lamblia

In this study we have reported the detailed characterization of a 58 kDa excretory–secretory product (ESP) of Giardia lamblia. The method of purification has been simplified which has improved the purification fold as well as the yield of the ESP. The binding efficacy of disialoganglioside (GD 2) to the purified ESP was found to be maximum among all other gangliosides used. The N-terminal sequence of the immunoreactive 29 kDa peptide obtained from partial tryptic digest of the ESP was found to be ADFVPQVST. The IgG against the purified ESP (IgG ES) showed cross-reactivity with the binding subunit of the commercially available cholera toxin and also with two protein bands of western cottonmouth moccasin snake toxin. The ESP could accumulate fluid in the intestine of sealed adult mice and also induce morphological changes in HEp-2 cells. The crude extract of G. lamblia trophozoites preincubated with Escherichia coli revealed 8-fold augmentation in the cytopathic activity on HEp-2 cells as compared to that of crude preparation from trophozoites only. Index Descriptors and Abbreviations: BSA, bovine serum albumin; OPD, O-phenylenediamine; HRP, horse radish peroxidase; FPLC, fast protein liquid chromatography; MEM, Eagle’s minimum essential medium; SDS–PAGE; sodium dodecyl sulfate polyacrylamide gel electrophoresis; kDa, kilodalton; GM 1, Galβ3GalNAcβ4(NeuAcα3)Galβ4Glcβceramide; GD 3, NeuAcα8NeuAcα3Galβ4Glcβceramide; GD 2,GalNAcβ4(NeuAcα8NeuAcα3)Galβ4Glcβceramide; GD 1a, NeuAcα3Galβ3GalNAcβ4(NeuAcα3)Galβ4Glcβceramide; GD 1b, Galβ3GalNAcβ4(NeuAcα8NeuAcα3)Galβ4Glcβceramide; GT 1b, NeuAcα3Galβ3GalNAcβ4(NeuAcα8NeuAcα3)Galβ4Glcβceramide

Campylobacter jejuni from patients with Guillain-Barré syndrome preferentially expresses a GD(1a)-like epitope.

GM(1)- and GD(1a)-like ganglioside mimicry in Campylobacter jejuni lipooligosaccharide (LOS) is considered to be involved in the pathogenesis of Campylobacter-induced Guillain-Barré syndrome (GBS). Compared with gastroenteritis-related isolates, GBS-related C. jejuni isolates were strongly associated with the expression of GD(1a)-like mimicry. The presence of a few genes involved in LOS ganglioside mimicry, cst-II, cgtA, and cgtB, was also associated with GBS-related strains. GD(1a)-like epitope expression may be an important virulence phenotype associated with the risk of developing GBS following campylobacter infection.

Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM

Cryosurgical ablation (CSA) of tumors induces disruptive necrosis. Necrosis may release tumor gangliosides into circulation and they may augment serum antiganglioside antibodies depending on the nature of gangliosides released. The hypothesis is tested by determining the level of serum total gangliosides (STG) and their antibody titers in the sera of colon cancer patients with cryoablated liver tumors. As controls, we examined the sera of patients who underwent radiofrequency ablation (RFA) and regular surgery (RS), none of which cause disruptive necrosis. The STG level (expressed as lipid-bound sialic acids, LBSA) is higher ( p 2<0.001) in 35 patients (stage IV) than in 38 healthy case-controls (median 23.48 mg/dL, Q-range 7.1 vs 16.04 mg/dL, Q-range 4.5). The mean STG level increased significantly to 31.2±6.0 mg/dL ( p 2<0.03) after CSA. Concomitantly, the IgM titer against colon cancer-associated gangliosides (GM 2, GD 1a, GT 1b), increased significantly, but no increase was observed against normal tissue gangliosides (GM 3 or GM 1). Also after RFA and RS, no such increase was observed either in the level of STG or in IgM titer against tumor gangliosides. The results suggest that CSA-induced necrosis might have acted as an adjuvant, because purified gangliosides without exogenous adjuvants even after repeated immunization failed to elicit antibody response. The post-CSA decline in the STG level correlated with the increase in the antibodies, suggesting a homeostatic role of the antibodies.

Enzymatic properties of sialidase from the ovary of the starfish, Asterina pectinifera

A sialidase [EC 3.2.1 18] was isolated and highly purified from the ovary of the starfish, Asterina pectinifera, and its enzymatic properties were compared with those of human placental sialidase. The final preparation gave one broad protein band corresponding to sialidase activity on polyacrylamide gel electrophoresis. The molecular weight of the enzyme was 360 000 by HPLC on Sigma Chrome GFC-1300 and Sephadex G-150 column chromatography, and 55 000 by SDS-PAGE, suggesting the presence of a hexamer in the native protein. The optimum pH was between 3.0 and 4.0, and the enzyme liberated sialyl residues from the following compounds: α(2-3) and α(2-6) sialyllactose, colominic acid, fetuin, transferrin, gangliosides GM 3, GD 1a and GD 1b. The enzyme was strongly inhibited by 4-aminophenyl and methyl thio-glycosides of sialic acid, but not by those glycosides of 5-amino sialic acid or sialic acid methyl ester. The enzyme was also highly inhibited by sulfated glucan and glycosaminoglycans. The substrate specificity and the effects of inhibitors on starfish sialidase were very similar to those of human placental sialidase.

Modifications of glycosphingolipid profile and synthesis in normal rat fibroblasts and in syngeneic neoplastic cells at different subculture stages

Glycosphingolipids are plasma membrane macromolecules involved in diversified recognition functions on the cell surface resulting in modulation of cell adhesion and differentiation. As the in vitro cellular system of the neoplastic cell line SGS/4A and syngeneic normal fibroblasts (FG) represents a useful tool for studies on molecular mechanisms regulating cell adhesion, neoplastic transformation and cellular ageing, we studied the changes of glycosphingolipid and of the enzymes involved in their metabolism in both cultured cells at different subculture stages. The FG subculture progression induces a drastic decrease of total glycosphingolipid content with consistent alterations in the molecular composition. In particular, a significant decrease of GM 3, a slight increase of GD 1a, the disappearance of ‘b’-series gangliosides and the drastic reduction of triosylceramides were observed. On the contrary, the increasing number of SGS/4A subcultures, characterized by a specific and different glycosphingolipid composition as compared with FG cells, does not cause modifications. Although glycosyltransferase activity levels quite well parallel the glycosphingolipid patterns and can account for the noted variations, the mRNA expression analysis of two glycosyltransferases suggests that the in vitro cell ageing of normal rat fibroblasts causes drastic changes in the glycosphingolipid profile through the regulation, at either the transcriptional or post-translational level, of some biosynthetic enzymes.

Complex gangliosides affect GD 3 accessibility to antibody in developing neuronal cells

Ganglioside expression of embryonic chick retina cells developed in vitro was analyzed by indirect immunofluorescence. Immature neurons were GD 3 positive cells and the labeling was chiefly distributed all over their cell membrane. Mature neurons became GD 3 negative and expressed complex gangliosides of the a- and b-pathways; nevertheless, the content of GD 3 accounted for approximately 40% of the total gangliosides in these cells. Neuraminidase hydrolysis pointed out that GD 3 was located in membrane of differentiated cells. The frequency of cells with the GD 3 immunostain localized in restricted areas of membrane of undifferentiated neurons increased significantly after adding a mixture of bovine brain gangliosides (largely complex gangliosides). Antibody binding to immobilized GD 3 showed a dose-dependent inhibition by adding a mixture of bovine brain gangliosides, GM 1, GD 1a or asialo-GM 1. Glycosphingolipids with shorter oligosaccharide chains, as cerebrosides or sulfatides, did not affect this binding. These results suggest that, concomitant with the accretion of content of complex gangliosides, a rearrangement in the membrane would occur, which progressively masks GD 3 to its antibody. This rearrangement might affect putative ganglioside functions involved in neuronal differentiation.

Modulation of the activity of Clostridium perfringens neuraminidase by the molecular organization of gangliosides in monolayers

The activity of Clostridium perfringens neuraminidase against gangliosides GM 3, GD 1a and GM 1 was studied in lipid monolayers at the air-buffer solution interface. The enzyme activity assay against pure ganglioside monolayers is based on the markedly different molecular packing areas of the substrate gangliosides and the resulting product glycosphingolipids. This allows to control and monitor the surface pressure and the ganglioside intermolecular organization (cross-sectional packing areas and dipole potentials) in a continuous manner during the catalytic process. It was found that the rate and the extent of the enzymatic reaction depended markedly on the lateral surface pressure. In general, the activity of neuraminidase against GM 3 and GD 1a was higher at lower surface pressure. This corresponded to larger intermolecular spacings among the ganglioside molecules. Both the activity and the extent of the reaction against GM 3 were higher than toward GD 1a. GM 1 could not be degraded by the enzyme, irrespective of the surface pressure but the enzyme could interact with this ganglioside. A latency period, longer for GM 3 than for GD 1a, was observed prior to the onset of rapid degradation; this indicates that pre-catalytic steps are occurring at the interface before effective ganglioside degradation takes place. The latency period, the total amount of ganglioside degraded, and the velocity of the reaction varied with the surface pressure in different manners. Our data indicate that the different steps of the catalytic reaction occurring at the surface (i.e., substrate recognition and interfacial adsorption, catalysis, maximum extent of substrate conversion) are independently regulated by the molecular organization of the substrate gangliosides.

Exogenously applied gangliosides (GM 1, GD 1a and G mix) fail to facilitate the induction of long-term potentiation (LTP) in the slices of hippocampus and superior colliculus of the guinea pig

To confirm the effect of gangliosides on the facilitation of the induction of long-term potentiation (LTP), slices of hippocampus and superior colliculus from guinea pig were prepared. One group of slices was incubated in the standard medium containing gangliosides (GM 1, GD 1a, or a mixture of gangliosides from bovine brain, each at a concentration of 70 μM) for 2 h. The other group of slices was incubated in the standard medium only. In both groups of slices, tetanic stimulation induced LTP in a similar manner. In low Ca 2+ (1 mM) medium, LTP was not induced in either group of slices. Thus, the present experiments could not confirm previous reports indicating that exogenously applied gangliosides facilitate the induction of LTP.

Ceramide composition of whole brain synaptosomal gangliosides from mice genetically bred for divergent ethanol sensitivities

A comparison of the two major ceramide molecular species (d18:1-C18:0 and d20:1-C18:0) of synaptosomal gangliosides GM 1, GD 1a + GT 1a, GD 1b, GT 1b, revealed a difference between the ceramide composition of ethanol-sensitive LS and ethanol-insensitive SS whole brain synaptosomal gangliosides. In all comparisons, the ratio of the two major molecular species, (d18:1-C18:0/d20:1-C18:0) was less for LS than for SS mice.

Calcium-ganglioside interactions and synaptic plasticity: effect of calcium on specific ganglioside/peptide (valinomycin, gramicidin A)-complexes in mixed mono- and bilayers

A controlled exchange of calcium between the extracellular space (mM Ca 2+) and the neuroplasm (μM Ca 2+) is considered to be an essential prerequisite for almost every stage of neuronal activity. Our research interest is focused on those compounds, which due to their physico-chemical properties and localization within the synaptic membrane might fulfill the task as neuromodulators for functional synaptic proteins. Because of this specific binding properties towards calcium and their peculiar interactions with calcium in model systems gangliosides (amphiphilic sialic acid containing glycosphingolipids) are favorite candidates for a functional involvement in synaptic transmission of information. In this study we used monolayers to investigate the molecular packing and surface potential at the air/water interface, the interaction of gangliosides with the depsipeptide valinomycin (= monovalent ion carrier), and its influenceability by calcium. Furthermore we looked at calcium effects on the single channel conductance and mean channel life-time of the monovalent ion channel gramicidin A in mixed PC/ganglioside bilayers. • — In pure ganglioside monolayers the addition of 0.01 mM Ca 2+ induces monolayer condensation, a rise in collapse pressure (= higher film stability), a shift of phase transition (= change of conformation), and a more negative head group potential (change of electric properties). • — In mixed ganglioside-valinomycin monolayers the addition of Ca 2+ causes phase separation and/or aggregate formation between the ganglioside and the peptide. • —Single channel conductance fluctuations as well as mean channel life-time were analyzed for gramicidin A incorporated into binary mixed black lipid membranes of negatively charged gangliosides (GM 1, GD 1a, GT 1b, G Mix) and neutral lecithin (DOPC) in different molar ratios. At monovalent electrolyte concentrations up to <250 mM CsCl the single channel conductance was significantly larger in the negatively charged mixed DOPC/ganglioside membranes than in the neutral DOPC membrane. Additionally, in the presence of gangliosides the mean channel life-time is increased. The addition of calcium (0.05 mM) induced a reduction of single channel conductance of gramicidin A in DOPC- and mixed DOPC/ganglioside membranes. These physico-chemical data in connection with new electronmicroscopical evidences for a precise localization of calcium, a calcium pump (Ca 2+-ATPase), a clustered arrangement of gangliosides in synaptic terminals, and biochemical results with regard to activatory nature of exogenous gangliosides for neuronal protein phosphorylation and ATPases, support the hypothesis of a modulatory function of gangliosides in synaptic transmission.

Isolation and characterization of the major glycosphingolipids from the liver of the rainbow trout ( Oncorhynchus mykiss): Identification of an abundant source of 9- O-acetyl GD 3

The carbohydrate structures of the major glycosphingolipids from the liver of the rainbow trout Oncorhynchus mykiss have been examined. We have isolated and identified four major neutral (glucosylceramide, galactosylceramide, lactosylceramide, and globoside) and five acidic (sulfatide, GM 3, GM 2, GD 1a, and 9- O-Acetyl GD 3) glycosphingolipids from trout liver. They have been characterized by 1H nuclear magnetic resonance spectroscopy, methylation analysis, fast atom bombardment mass spectrometry, and specific monoclonal antibodies. Significantly, the relatively scarce ganglioside 9- O-acetyl GD 3 was found to comprise approximately 23% of the total ganglioside content of normal rainbow trout liver. 9- O-Acetyl GD 3 is, however, abundant in human melanoma and as such, trout liver may be a suitable source of this antigen.

Ganglioside biosynthesis in rat liver: Different distribution of ganglioside synthases in hepatocytes, kupffer cells, and sinusoidal endothelial cells

The activities of five glycolipid-glycosyltransferases, GL 2, GM 3, GM 2, GM 1, and GD 1a synthase, were determined in a cell-free system with homogenate protein of total rat liver, isolated hepatocytes, Kupffer cells, and sinusoidal endothelial cells. In rat liver parenchymal and nonparenchymal cells ganglioside synthases were distributed differently. Compared to hepatocytes, Kupffer cells expressed a nearly sevenfold greater activity of GM 3 synthase, but only 14% of GM 2, 19% of GM 1, and 67% of GD 1a synthase activity. Sinusoidal endothelial cells expressed a pattern of enzyme activities quite similar to that of Kupffer cells with the exception of higher GM 2 synthase activity. Activity of GL 2 synthase was distributed uniformly in parenchymal and nonparenchymal cells of rat liver, but differed by sex. It was 1 to 2 orders of magnitude below that of all the other ganglioside synthases investigated. The results indicate GL 2 synthase regulates the total hepatic ganglioside content, and hepatocytes but not nonparenchymal liver cells have high enzymatic capacities to form a-series gangliosides more complex than GM 3.

Effects of intraventricularly applied gangliosides and N-acetylneuraminic acid on acquisition and retention performance of a brightness discrimination task in rats

The effects of intraventricularly applied gangliosides (about 90 to 120 nmoles/10 μl) and N-acetylneuraminic acid (800 nmoles/10 μl) on acquisition and retention of a brightness discrimination task were studied in rats. Single injections of GT 1b and N-acetylneuraminic acid improved the retention performance. GM 1 showed an enhancing effect on both acquisition and retention, while GD 1a and GD 1b exerted no influence on the behavioral parameters tested. The findings presented show how memory may be improved by exogenous application of substances commonly occurring in the mammalian body.

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: GM 3, GM 1, GD 3, GD 1a, and GT 1b. The same gangliosides plus ganglioside G x, the chromatographic mobility of which corresponded to the mobility of ganglioside GD 1b 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 GM 3 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 GM 3 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.

Gangliosides suppression of murine lymphoproliferation and interleukin 1 production

Studies were carried out to determine whether inhibition of gangliosides on lymphoproliferation was related to interleukin (IL)-1. The results showed that gangliosides, GM 1 and GT 1b were able to inhibit the proliferation of spleen lymphocytes from C57BL/6J mice in dose-dependent fashion, whereas asialo-GM 1 was not inhibitory. However, gangliosides, GM 1 and asialo-GM 1 did not suppress the production of IL-1 in Salmonella typhosa lipopolysaccharide (LPS)-induced peritoneal adherent cells. Various types of LPS including S. enteritidis, S. minnesota and Escherichia coli 055:B5 were used to stimulate the production of IL-1 in adherent cell cultures. The IL-1 production was not affected by gangliosides, GD 1a and GD 1b. Although GT 1b supressed IL-1 production of human monocytes to 82% of control level it did not, however, affect the IL-1 production of murine adherent cells. Thus, the inhibitory mechanism of gangliosides on murine immune cells remains unclear, and warrants further study.